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APPLICATION FILE
Call for applications 2012
Certification of sites dedicated to integrated
research in cancer
- SIRIC -
Consortium ONCO Lille
Application file
Nom de l’établissement candidat
C2RC Lille
CHRU & Centre Oscar Lambret
Nom du directeur du projet SIRIC
Pr. Eric Lartigau
Etablissements partenaires
CHRU of Lille
Centre Oscar Lambret
Université(s) de référence
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SIRIC - CALL FOR APPLICATIONS 2012
PRES Lille Nord de France
APPLICATION FILE
C
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T
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I. General presentation
10
I.1. HISTORICAL BACKGROUND OF THE COOPERATION
I.1.1.
T
10
ONCO LILLE CONSORTIUM: A STRONG EXISTING PARTNERSHIP BETWEEN
10
ACADEMIC HOSPITALS
I.1.2.
ONCO LILLE:
EUROPEAN
STATE
OF
THE
ART
FACILITIES
IN
BASIC,
TRANSLATIONAL AND CLINICAL RESEARCH IN ONCOLOGY
11
ONCO LILLE: A DYNAMIC ENVIRONMENT FOR INNOVATION AND INTEGRATION
12
I.2. Presentation of the partner organisation and their major assets
I.3. Strategic considerations for ONCO Lille
14
35
I.1.3.
I.3.1.
A RESPONSIBILITY, A VISION AND AN AMBITION
35
I.3.2.
THE RESEARCH FACILITIES
40
I.3.3.
TOWARD AN INTEGRATED RESEARCH CENTRE
41
I.3.4.
MANAGEMENT AND ORGANIZATION OF THE SIRIC SCIENTIFIC ISSUES
42
I.3.5.
CONTRIBUTION TO THE OBJECTIVES OF THE PLAN CANCER II
42
I.3.6.
INTERNATIONAL COLLABORATIONS
42
I.3.7.
VALORISATION STRATEGY
43
I.3.8.
DISSEMINATION STRATEGY
43
I.3.9.
CONCLUSION
43
II. Presentation of the medical, scientific and technological
potential of the SIRIC
44
II.1. Medical activity
II.1.1.
CHRU LILLE
44
II.1.1.1.
ORGANIZATION OF CANCER TREATMENT AT THE CHRU
45
II.1.1.2.
CANCER TREATMENT
46
II.1.2.
CENTRE OSCAR LAMBRET
II.2. Research activity
II.2.1.
FUNDAMENTAL SCIENCES
47
49
49
II.2.1.1.
BIOLOGY
49
II.2.1.2.
RESEARCH IN HUMAN AND SOCIAL SCIENCES AND PUBLIC HEALTH
51
II.2.2.
3
44
CLINICAL RESEARCH
52
II.2.2.1.
CHRU LILLE
52
II.2.2.2.
CENTRE OSCAR LAMBRET –THE CLINICAL RESEARCH UNIT
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APPLICATION FILE
II.2.3.
TRANSLATIONAL RESEARCH
II.3. Presentation of the SIRIC shared resources and facilities
57
58
II.3.1.
4 INTEGRATED PLATFORMS
58
II.3.2.
INTEGRATED PLATFORM 1: BIOLOGY
59
II.3.3.
INTEGRATED PLATFORM 2: IMAGING
66
II.3.4.
INTEGRATED PLATFORM 3: ANIMAL MODELS
74
II.3.5.
INTEGRATED PLATFORM 4: CLINICAL RESEARCH AND METHODOLOGY
81
III. Integrated research programs
III.1. Overview of the two integrated programs
III.2. Tumour and host resistance to loco-regional treatments
91
91
93
III.2.1. MAJOR THEME OF THE PROGRAM
94
III.2.1.1.
MEDICAL RATIONALE AND SCIENTIFIC OBJECTIVES OF THE PROGRAM
94
III.2.1.2.
METHODOLOGICAL BACKGROUND
95
III.2.1.3.
ASSETS OF LILLE’S TEAMS
96
III.2.1.4.
TEAMS, INSTITUTIONS AND INFRASTRUCTURES INVOLVED IN PROGRAM 1
99
III.2.2. MAIN TARGETS OF THE PROGRAM’S WORK
100
III.2.2.1.
BASIC RESEARCH
100
III.2.2.2.
TRANSLATIONAL RESEARCH
105
III.2.2.3.
CLINICAL RESEARCH
109
III.2.2.4.
CONTRIBUTION OF HUMAN AND SOCIAL SCIENCES
114
III.2.3. EXPECTED RESULTS
III.2.3.1.
IN TERMS OF PRODUCTION
III.2.3.2.
IN TERMS OF DISSEMINATION OF KNOWLEDGE AND OF PROVISIONAL
CALENDAR
119
119
120
III.2.4. FOCUS ON THE EMERGING RESEARCH ASPECTS THAT MAY BENEFIT FROM
FUNDING OF THE SIRIC
III.2.5. APPENDICES
III.2.5.1.
122
INTEGRATION WITHIN THE WHOLE SCIENTIFIC PROJECT – ARTICULATION
WITH THE OTHER PROGRAMS
122
III.2.5.2.
PLANNING
123
III.2.5.3.
BUDGET
124
III.3. Tumour dormancy and persistence
III.3.1. MAJOR THEME OF THE PROGRAM
4
121
125
126
III.3.1.1.
SCIENTIFIC OBJECTIVES OF THE PROGRAM
126
III.3.1.2.
METHODOLOGICAL BACKGROUND
126
III.3.1.3.
TEAMS, INSTITUTIONS AND INFRASTRUCTURES INVOLVED IN PROGRAM 2 127
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III.3.2. MAIN TARGETS OF THE PROGRAM’S WORK
128
III.3.2.1.
BASIC RESEARCH
128
III.3.2.2.
TRANSLATIONAL RESEARCH
134
III.3.2.3.
CLINICAL RESEARCH
137
III.3.3. EXPECTED RESULTS
138
III.3.4. FOCUS ON THE EMERGING RESEARCH ASPECTS THAT MAY BENEFIT FROM
FUNDING OF THE SIRIC
139
III.3.5. APPENDICES
141
III.3.5.1.
PLANNING
141
III.3.5.2.
BUDGET
141
IV. National and international collaborations program
142
IV.1. Role in regional and national clinical research
142
IV.2. International networks and collaborations
143
IV.3. Strategy of the SIRIC for national and international collaboration 144
V. Partnership and valorisation strategy
146
V.1. Strategy and priorities
V.2. Strategy implementation
146
146
V.2.1. THE TECHNOLOGY TRANSFER ORGANISATION IMPLEMENTED IN THE SCOPE OF
ONCO LILLE
V.2.1.1.
THE FRAME OF THE COOPERATION WITHIN LILLE UNIVERSITY HOSPITAL
AND CENTRE OSCAR LAMBRET
V.2.1.2.
146
146
THE FRAME OF THE COOPERATION WITH THE SATT NORD DE FRANCE
VALO AND EURASANTE
V.2.2. KEY STRATEGIC ACTIONS
147
147
V.2.2.1.
TRANSFORM RESEARCH INVESTMENT INTO IP
147
V.2.2.2.
DEVELOPING AN EFFECTIVE PARTNERSHIP STRATEGY WITH INDUSTRY
147
V.2.2.3.
DEVELOPING A COMMUNICATION AND DISSEMINATION STRATEGY THAT
WILL ENHANCE ONCO LILLE ATTRACTIVENESS AND PROFILE: ONCO LILLE
AS A LEADING EUROPEAN ONCOLOGY RESEARCH INSTITUTE
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150
V.2.3. LINKS WITH TECHNOLOGY TRANSFER STRUCTURES (SATT)
150
V.2.4. LINKS WITH COMPETITIVENESS CLUSTERS
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VI. Knowledge and practices dissemination program
VI.1. Spreading excellence, dissemination knowledge
VI.2. Dissemination to the professionals
VI.2.1. EXISTING DISSEMINATION PROGRAMS
152
152
154
154
VI.2.1.1.
ACADEMIC TEACHING
154
VI.2.1.2.
PROFESSIONAL TRAINING
154
VI.2.2. TOOLS TO BE IMPLEMENTED
155
VI.2.2.1.
DEVELOPMENT OF MASTER DEGREES
155
VI.2.2.2.
DEDICATED WEB PAGE
155
VI.2.2.3.
ONCO LILLE SCIENTIFIC SEMINARS
156
VI.3. Dissemination to the patients and the public
156
VI.3.1. ACTION OF THE REGIONAL COUNCIL “THE WEEK AGAINST THE CANCER”
156
VI.3.2. COMMUNICATION TO THE PATIENTS
156
VII.Organisation and management of ONCO Lille activities 158
VII.1. Director
VII.2. Administrative and Managerial organisation
VII.2.1. ONCO LILLE PROJECT GENERAL STRUCTURE
VII.2.1.1. STRATEGIC AND GOVERNANCE MANAGEMENT:
159
161
VII.2.2. INTERNATIONAL SCIENTIFIC COMITTEE
162
VII.2.2.1. MANAGEMENT OF ONCO LILLE
162
VII.3. Scientific organisation and management
VIII.
158
159
164
VII.3.1. SCIENTIFIC STEERING COMMITEE
165
VII.3.2. MANAGEMENT TOOLS TO BE IMPLEMENTED - ACTION PLAN
165
Budget
167
VIII.1.
ONCO Lille operating previsional budget
167
VIII.2.
Funding from the SIRIC call to the scientific programs
169
VIII.3.
Funding of the SIRIC call for management, collaboration,
valorisation, and dissemination
169
VIII.4.
Funding already obtained by SIRIC researchers:
169
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Administrative part
I. Fiches signalétiques
173
II. Engagements et Signatures
175
II.1.
II.2.
II.3.
II.4.
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Directeur du projet SIRIC
Etablissement candidat
Engagement et signatures des universités de référence
Engagement et signatures des partenaires
SIRIC - CALL FOR APPLICATIONS 2012
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176
177
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APPLICATION FILE
Résumé du projet ONCO Lille
En France, l'incidence des cancers est d'environ 320 000 nouveaux cas par an. La comparaison avec les différents
registres nationaux montre que la région Nord – Pas de Calais présente la plus forte incidence au niveau national,
le taux de mortalité par cancer dans cette même région étant l'un des plus fort en Europe. De plus notre région,
avec son passé industriel (mines, textile, sidérurgie...) présente encore de grandes disparités sociales avec un taux
très élevé de chômage.
Cette situation médico sociale unique a fait que les deux hôpitaux académiques de Lille, le CHRU et le Centre de
Lutte contre le Cancer (CLCC Oscar Lambret) se sont unis dès 2005 afin de développer une politique médico
scientifique commune dans un Groupement de Coopération Sanitaire (GCS) : le Centre Régional de Référence
en Cancérologie (C2RC). Cette collaboration soutenue par le Conseil Régional, les Universités et les EPST (CNRS,
INSERM...) a permis la mise en œuvre de nombreux travaux dans le champ de la recherche fondamentale,
clinique et des sciences humaines et sociales. De ce fait la communauté scientifique lilloise à une très grande
légitimité pour répondre à l'appel à projets Siric 2012 dans le cadre du plan cancer 2 (2009-2013).
Le consortium ONCO Lille regroupe des acteurs de premier plan de la recherche clinique et fondamentale
(laboratoires labellisés A+ et A) avec des programmes particulièrement innovants dans les domaines de la
génomique, protéomique, banque des tumeurs, modèles animaux, imagerie et méthodologie de la recherche
clinique. Les chercheurs impliqués sont des leaders reconnus dans leurs domaines de compétence. Pour toutes
ces raisons, ONCO Lille développe un projet original en recherche intégrée sur 2 questions essentielles de la
cancérologie moderne : la résistance de la tumeur et de l'hôte aux traitements loco- régionaux et la
dormance/persistance tumorale après traitement. Cette recherche est base sur les compétences des acteurs de
la recherche fondamentale et sur la fréquence ou l'agressivité des modèles cliniques choisis (oesophage, foie,
plèvre, gynécologie, hématologie et prostate.) faisant l'objet de programmes de recherche clinique sur le site.
Programme1 : resistance de la tumeur et de l'hôte aux traitements loco-régionaux dans les tumeurs ORL,
oesophagiennes, hépatiques et gynécologiques.
Programme 2 : dormance et persistance tumorale dans les hémopathies, le mélanome et le cancer de la
prostate.
Ces programmes originaux reposent sur des données provenant des travaux des équipes du site avec de
potentielles retombées très importantes pour une meilleure prise en charge de nos patients. Ils intègrent des
données provenant de la recherche fondamentale, de la recherche translationelle, de la recherche clinique et
des sciences humaines et sociales, en particulier pour améliorer le suivi individuel et collectif des patients.
La diffusion des connaissances se fera principalement en direction des médecins généralistes, de manière à
produire des recommandations sur l'adaptation personnalisée du suivi et de la réinsertion professionnelle des
patients. À travers une étroite collaboration avec les facultés de médecine, de pharmacie et sciences
biologiques, la diffusion des connaissances se fera à travers les différents cycles de formation, et notamment les
master.
De nombreuses collaborations ont d‟ores et déjà été développées avec des entreprises de biotechnologie
régionales et nationales à travers Eurasante. ONCO Lille s‟appuie sur de nombreux partenariats existant avec des
équipes de recherche fondamentale et clinique, en France (cancéropôle Nord Ouest) et à l‟international
(Belgique, Hollande) : une stratégie spécifique visera à renforcer et développer de nouvelles coopérations.
ONCO Lille va apporter de nouvelles connaissances sur la résistance aux traitements et la persistance après
traitement. L'originalité de cette démarche, totalement intégrée, regroupant toutes les facettes de la recherche
en cancérologie, est d'apporter des informations essentielles en adaptation thérapeutique dans le cadre l’une
médecine personnalisée.
Du fait de l'incidence particulière dans notre région, ces programmes ont une indiscutable réalité clinique. Basés
sur une expérience de collaboration de plus de 5 ans, regroupant tous les acteurs de la cancérologie et soutenu
par les politiques régionaux, ONCO Lille représente une réelle opportunité pour développer un centre de
recherche intégrée sur le cancer de référence au niveau européen.
Montant demandé pour 5 ans
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SIRIC - CALL FOR APPLICATIONS 2012
7,7 Millions d’Euros
APPLICATION FILE
Summary of the ONCO Lille project
In France, the number of new cancer cases is approximately 320,000 yearly. In comparison with data
obtained by various departmental French cancer registries, the Nord – Pas de Calais region displays
the highest rate of cancer incidence and mortality in France and one of the highest in Europe.
Furthermore, the region, with its historical background of heavy industries (coal mines, steel and textile
mills, etc…) is characterized by high level of unemployment, social grants and limited resources. This
unique social and clinical situation spurred the two regional academic centres, the C.H.R.U. (Centre
Hospitalier Régional Universitaire) and the Cancer Centre (Centre Oscar Lambret) to combine their
efforts in 2005 so as to develop a common medical policy (C2RC: centre de référence regional en
cancérologie) in the field of oncology. This collaboration, strongly backed by the Regional Council, has
generated a large body of shared scientific research in biology, medicine and human sciences in
association with the CNRS, INSERM and the Universities.
As a result, our scientific and medical community is legitimate to answer and fulfil the INCa tender,
within the framework of Plan Cancer 2 (2009-2013).
The ONCO Lille Consortium brings together outstanding strengths of researchers in basic, translational
and clinical research (labelled A+ and A teams) with very successful developments (genomic,
proteomic, tumour bank, animal models, imaging, methodology...). The core members of ONCO Lille
are recognised as international leaders in their field of competence. For all these reasons, ONCO Lille
develop an original project aiming to achieve state of the art integrated research in some of the most
important issues for oncology: tumour resistance and persistence after loco-regional treatments. Based
on a large number of clinical and fundamental research programs in aggressive diseases
(oesophagus, liver, melanoma, head & neck...) or most common diseases (prostate, gynaecology,
haematology…), and on the existing level of excellence, the 2 integrated programs are:
Program 1: tumour and host resistance to loco regional treatments in the field of head and neck,
oesophagus, liver and gynaecological tumours.
Program 2: tumour dormancy and persistence in the field of haematology, melanoma and prostate
cancer.
They have the originality to stand on very strong basic or clinical research and to be able to achieve
significant breakthroughs in the modelling of resistance to initial treatment and recurrence after
treatment for the benefit of patients and healthcare providers.
All programs will integrate biological research, translational research, innovative imaging, clinical
research and humans sciences developments, particularly in the field of comprehensive handling of
the disease for the patient and the family (global care). Dissemination of knowledge will be directed
towards patients in the field of adapted follow up and professional reinsertion, as well as towards
general practitioners and political authorities. Through a close collaboration with the faculty of
medicine & the faculty of pharmacy and biological sciences, the most valuable results will be
integrated in teaching (masters). Numerus cooperations have been already developed with local and
regional biotech companies through the Eurasanté Incubator. Furthermore the existing regional
(Cancéropôle Nord Ouest) and international (Belgium, Netherlands,...) cooperations will be strongly
reinforced.
The consortium ONCO Lille will bring new data on the mechanisms of resistance and persistence to
treatment in human tumours. Bringing together such information in biological models, imaging and
clinical research will help to drive new studies in the field of adaptive and personalised medicine. Due
to the specific cancer incidence in our region, this proposal has clinical reality.
Based on the past 5 years‟ history of integrated research, together with the involvement of all players in
cancer care and strong political commitment, our project provides a real opportunity to implement a
truly comprehensive cancer centre in north of France.
Requested amount for 5 years
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SIRIC - CALL FOR APPLICATIONS 2012
7.700 million Euros
APPLICATION FILE
ONCO Lille project
I.
I.1.
General presentation
HISTORICAL BACKGROUND OF THE COOPERATION
I.1.1. ONCO LILLE CONSORTIUM: A STRONG EXISTING PARTNERSHIP BETWEEN ACADEMIC
HOSPITALS
In France, the number of new cancer cases is approximately 320,000 yearly. When referring to
data obtained by various departmental French cancer registries, the Nord – Pas de Calais region
displays the highest rate of cancer incidence and mortality. In 2005, the incidence in the Nord –
Pas de Calais of head and neck as well as oesophagus cancers in the male population was
twice the national incidence. In such, Lille is the capital city of the region having the highest
incidence and over mortality in cancer, region characterized by a high proportion of
unemployment, social aids and limited resources. Most of these cancers can be considered as
preventable, as they are linked to behaviour (tobacco, alcohol), environmental factors
(industries), socio-economical conditions or more rarely to genetic familial factors. Local,
regional and systemic recurrences are common and often associated with secondary and/or
new primaries due to the same risk factors.
This social and clinical reality has motivated the two academic reference oncology centres, the
Centre Hospitalier Régional et Universitaire (C.H.R.U., www.chru-lille.fr) and the Centre Régional
de lutte contre le Cancer (Centre Oscar Lambret, COL, www.centreoscarlambret.fr) to start a
cooperation in 1999 and to sign a formal collaboration agreement in 2005 for developing a
common medical policy (C2RC : centre de référence regional en cancérologie) in the field of
oncology with the set up of fundamental and clinical research programs. This collaboration was
developed in the framework of a large community of scientific research in biology and human
sciences, strongly supported by the regional council in the fields of training and equipments.
The C.H.R.U. and the COL are leading hospitals for cancer care and research:
the CHRU is the largest academic hospital of France with the largest faculty of medicine ;
the centre Oscar Lambret is the second cancer centre for clinical research (Details are given
in chapter 2).
The C2RC is developed around a medical conference including 46 physicians (23 from the CHRU
and 23 from the Cancer centre). The medical programs have been integrated in between the
two hospitals and are based on common or shared platforms. This organization makes the
collaboration, around the patients, a clinical reality. All aspects of biological, translational and
clinical research are considered in C2RC. Lille C2RC is today one of the rare fully integrated
cancer patient network in France.
ONCO Lille Consortium is based on the historical collaboration of the C2RC together with new
members (funding members, see 2) with scientific actions in the national framework of Plan
cancer 2. A cooperation protocol is already signed in between Universities, Inserm, CNRS and
the academic hospitals.
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APPLICATION FILE
In plan cancer 2, a specific emphasize has been made on social inequalities and access to
care. These issues are particularly important in the social environment of Lille as stated above.
Future programs and collaborations developed are in the framework of already very strong local
collaborations in the public Health and Biomedical research Committee (Comité de la
Recherche Biomédicale et en Santé Publique) with 4 axes:
Cardio-vascular and metabolism
Inflammation & immunology
Neurosciences
Cancer
The next step through SIRIC is to secure this organization and develop new research programs
oriented to Human Sciences, biology, clinical research and the production of recommendation
for patients care
I.1.2. ONCO LILLE: EUROPEAN STATE OF THE ART FACILITIES IN BASIC, TRANSLATIONAL AND
CLINICAL RESEARCH IN ONCOLOGY
One of the success factors in the C2RC has been the mutualisation of expertise to be successful
at national levels as for:
multidisciplinary meetings for treatment decision working with physicians from the 2 hospitals
platforms (see above),
education and training.
This has been particularly demonstrated in some pilot activities like:
Cancer registry of Lille and its region: the cancer registry is integrated in the C2RC from
January 1st 2009. The data are collected from 35 sources (pathology, DIM, health authorities,
private centres, biology laboratories…). In 5881 cases have been validated and results
published (www.registrecancers59.fr).
Common tool for the analysis of oncology activity – OncoDIM: since 2001, the professionals of
the two “Départements d‟information médicale” have developed a common tool to analyse
and describe the activity in oncology of the two hospitals and of the other regional hospitals
or clinics. This action has been strongly supported by the regional health authority (ARH-ARS)
and by the Regional Council.
Pilot clinical programs:
-
-
Aging: a pilot unit has been developed and is labelled by the INCa.
Paediatrics: onco-haematology is treated in the CHRU and solid tumours at the COL. The
two Departments are reference centres and are the coordinators of the regional
multidisciplinary clinic.
Bone metastases and sarcomas: due to the requested multidisciplinary approach (surgery,
pathology, medical and radiation oncology, these two clinical situations have been totally
integrated by the C2RC. The sarcoma clinic is labelled by INCa.
ONCO Lille brings already together many platforms in the field of research and care, as for
example a tumour bank (labelled by INCa with more than 100, 000 specimen) or robotic
equipments (Robotic surgery with a Da Vinci Surgical robot, CyberKnife implemented in 2007
after a successful answer to a National cancer Institute national tender with more than 1000
patients treated).
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APPLICATION FILE
 Clinical research
Clinical research programs are shared in between the two hospitals. More than 250 trials are
continuously ongoing. The integrated clinical research unit from the COL and the Clinical
Investigation Centre (CIC/Inserm) from the CHRU have signed a cooperation agreement in 2009.
 Training
Within the framework of the largest medical school in France, the C2RC training policy allows the
organization of many educational and training programs. For example:
Yearly « Régionales de Cancérologie » workshop
Regional oncology network
Education of clinical research technicians
Training of medical students and internes …
I.1.3. ONCO LILLE: A DYNAMIC ENVIRONMENT FOR INNOVATION AND INTEGRATION
This collaboration, strongly backed by the Regional Council with grants for equipments and
training programs, has generated a large body of shared scientific research in human sciences,
biology and medicine. In association with the CNRS, INSERM, University.... ONCO Lille gathers
outstanding strengths researchers in basic, translational and clinical research (several A+ and A
team or researchers).
The interactions have been made possible by the geography with all teams located on the
medical campus (13 000 employees) and close to the Universities and associated research
campus (Pasteur, IBL...).
GEOGRAPHICAL Situation of the Partners
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APPLICATION FILE
The specificity of the cancer incidence made the cooperation a necessity and a reality in order
to be able to tackle the enormous challenge of taking care of our patients in all aspects:
research, treatment and socio professional reinsertion. A very good example is our tumour bank
which, in 2009, recieved the highest national ranking for scientific contributions .
As a result, our medical and scientific community is now particularly suited to answer and fulfil
the INCa tender, our project complying totally with the framework of Plan Cancer 2 (2009-2013).
All the partners are strongly convinced of our legitimacy to become a SIRIC. The funding
members are listed below.
Based on the past 5 years‟ history of integrated research, together with the involvement of all
players in cancer care and strong political commitment, our project provides a real opportunity
to implement a truly comprehensive cancer centre in the North of France.
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APPLICATION FILE
I.2. Presentation of the partner organisation and their major
assets
CHRU
Management
M Yvonnick MORICE, General Manager of the CHRU de Lille
Contact
 Ms Floriane BOUGEARD, Manager of the Federation of Oncology
 2, avenue Oscar Lambret – 59 037 Lille Cedex
 00 33 3 20 44 59 62
Key figures / Key features
The Centre Hospitalier Regional Universitaire of Lille (CHRU) is a public institution and the only University
Hospital of the Nord-Pas de Calais area (4 million inhabitants – 7% of the french population). It is the regional
reference platform for most medical, surgical and technical activities.
The campus of the University Hospital is vast and includes on one single location: 12 specialized hospitals, 3
universities (Medicine, Dental and Pharmacy). The Centre Oscar Lambret, dedicated to cancer treatment, is
located nearby, which ensures close links between them.
Key figures:
 2 965 beds
 13,500 employees (including 3000 physicians)
 Receive 120,000 Emergencies each year
 Yearly 93 483 in-patients and 1,192 290 outpatient
 Annual budget : 950 millions €
The CHRU dispose of many assets, including the latest and most advanced equipments such as platforms in
imaging (6 MRI’s including 1 dedicated to research, 12 CT scans, 7 digital angiographies, 7 gamma cameras, 1
TEP), surgical facilities ( 80 OR, 16 surgical lasers, 1 Stereotactic radio-surgery Gamma-Knife ®…) and a biologypathology Centre including 23 laboratories providing modern diagnosis technologies.
Team involved in ONCO Lille
Laboratory of cellular haematology, Dermatology hospital, Urology service, Gynecology department, Head and
neck cancer department, Medical oncology department, Department of digestive and oncological surgery,
Gastroenterology and hepathology department, General and Digestive surgery, Pneumology and chest
oncology, EA 2694 (Health economy), Clinical research unit, Institute of Pathology, Centre of BiologyPathology, Inserm U703, Imaging Department, Service of Urological, Head and Neck and Hematological
Radiology, Environment and professional pathologies department, CRDPD EA, Geriatrics department
Description (skills & resources)
The coordination of the oncology activities is ensured by the "Federation of Oncology ", which constitutes an internal
network support, promoting a multidisciplinary yet integrated care for the diagnosis and treatment of cancer patients.
The Federation promotes patient support and encourages the emergence of innovative activities and scientific
projects in the field of malignancies, and in particular the collaborations with Northwest Cancéropôle
fundamental research units and laboratories.
The Federation of Oncology from CHRU participates, in connection with the Faculty of medicine - including its
continuous medical education Department and Centre Oscar Lambret - to theoretical and practical teaching as
well as continuing education for physicians, medical students and staff.
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SIRIC - CALL FOR APPLICATIONS 2012
APPLICATION FILE
Main assets for ONCO Lille
The CHRU de Lille is the first institution within the north west interregion for cancer patients with 9 976 inpatients hospitalized in 2010 (95% of adults and 5% of children). Among them 70 to 75% are new patients.
Cancer patients represent 16.2% of hospital stays of the CHRU corresponding to 29 251 stays in year 2010.
th
rd
The CHRU de Lille is the 4 university hospital in France in terms of scientific publications, the 3 in clinical
research :
a) On the period 2006-2010, the scientific publications in haematology realized by the establishment
represented 10% of the publications written in France in this field, but 14.4% of the citations. In oncology, 3.7%
of the publications and 5.7% of the citations (Data issued from Incites/Web of Science – Thomson Reuters).
Haematology and oncology are, in terms of citations, the first and third disciplines :
b) Number of trials and number of included patients: each year, the CHRU de Lille sponsors nearly 70 new
studies and is investigator centre in nearly 900 studies (academic and industrial). In 2010, more than 4000
patients have been included in clinical trials. The participation of patients with cancer to clinical trials has
increased of 40% between 2009 and 2010, reaching 1113 patients in 2010 for 322 active clinical trials both
academic and pharmaceutical companies driven.
Oncology represents nearly 20% of research activities and is one of the 4 main axis of research of the
establishment.
CHRU of Lille will support and participate in SIRIC project, through research teams, technological equipment
and active file of patients.
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APPLICATION FILE
Centre Oscar Lambret
Management
Bernard Leclercq, General Director
Contact
 Tel: +33 (0)3 20 29 59 59
 3 rue F. Combemale, 59000 Lille
 http://www. centreoscarlambret.fr
Key figures / Key features
The Centre Oscar Lambret (COL) is the cancer centre of the Nord Pas de Calais area. The COL is member of
Unicancer group as well the 17 others cancer centres in France.
The 3 missions of the institution are: care, teaching and research. Values are: multidisciplinarity, development
of medical progress through research and innovation and optimal care to the patient and his family.
Key figures:
 780 employees
 210 beds and places
 Every year: 16 000 patients treated, 37 000 days in-hospital, 45 000 medical consultations, more than
50 000 radiotherapy fractions and 10 000 chemotherapy in out patient hospital.
 Annual budget: 78 millions €
More than 1800 patients are treated annually for breast cancer, 900 patients for head and neck cancer, 500
patients for gynecological cancer, 500 patients for digestive cancer, 350 patients for lung cancer, 300 patients
for urological cancer, 200 patients for soft tissue sarcoma and about 120 patients with pediatric cancer.
The institution has a large and innovative technical support: a surgical robot (Da Vinci), a platform of imaging
including 1 IRM 3T, TEP scan, 2 gamma cameras, 3 ultrasound, one mammotome), a large radiotherapy
platform (2 varian Clinac, 1 Primus Siemens, 2 tomotherapy, 1 Cyberknife) and brachytherapy equipment (1
HDR and 3 PDR).
Team involved in ONCO Lille
Digestive and Urology department, Head and neck cancer department, Pneumology,chest and sarcoma
departement, Radiotherapy department, U837 (cellular and molecular targeting for cancer treatment), Clinical
research unit, Methodology and Biostatistic Unit and the platform of Biology-Pathology
Description (skills & resources)
The coordination of the oncology activities is ensured by the 3C promoting a multidisciplinary integrated care
for the diagnosis and treatment of cancer patients.
It participates with the Federation of Oncology from the CHRU, in connection with the Faculty of medicine to
theoretical and practical teaching as well as continuing education for physicians, medical students and staff.
Main assets for ONCO Lille
The COL is the third CLCC in term of clinical research with more than 700 patients included in clinical trials (13%
of the active file of patients).
In 2010, 158 phase 1 to 3 clinical trials have been activated with 66% of academic studies. 19 PHRC (Programme
hospitalier de recherche Clinique) have been funded and sponsored by the COL since 2003.
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APPLICATION FILE
Centre de Référence Régional en Cancérologie (CRRC)
Management
Françoise Weingertner – Director
Contact
 Tel: +33 (0)3 XX 20 44 47 40XX XX XX
 2, avenue Oscar Lambret – 59 037 Lille Cedex
 http://www. http://www.centreoscarlambret.fr/accueil/menumilieu/le-centre-oscar-lambret/centre-regional-de-reference-encancerologie.html
Key figures / Key features
The Health-care cooperation group « Centre de Référence Régional en Cancérologie » (C2RC for regional
reference centre in oncology) was created by CHRU of Lille and the Centre de Lutte Contre le Cancer, Oscar
Lambret (COL). The objective of the cooperation is the preparation and the implementation of a common
medical and scientific project in oncology.
Focused on innovation, the first medical and scientific project allowed implementing innovative techniques and
procedures of medical care.
Team involved in ONCO Lille
CHRU: Laboratory of cellular hematology, Dermatology hospital, Urology service, Gynecology department, Head
and neck cancer department, Medical oncology department, Department of digestive and oncological surgery,
Gastroenterology and hepathology department, General and Digestive surgery, Pneumology and chest
oncology, EA 2694 (Health economy), Clinical research unit, Institute of Pathology, Centre of Biology-Pathology,
Inserm U703, Imaging Department, Service of Urological, Head and Neck and Hematological Radiology,
Environment and professional pathologies department, CRDPD EA, Geriatrics department
COL: Urology and digestive oncology department, Head and neck cancer department, Methodology and
biostatistic unit, Clinical research unit, Laboratory of Human Molecular Oncology, Service
Description (skills & resources)
Lille site acquired, through this strenghtened cooperation, hightech equipments like the Gamma-knife, the
Cyber-knife, a surgical robot or a laser ureteroscope. The group manages also the tumor library, the regional
centre of molecular pathology and the platform of molecular biology which benefit from the INCa support. The
activity of molecular biology is interregional and for many tests national and international. To ensure
sustainable development, the C2RC invested in high-rate sequencing.
Medical teams of COL and CHRU collaborate in the framework of the C2RC to implement coordinated and
multidisciplinary actions. For instance, the medical care of sarcoma, bone or brain metastasis, oncopediatry and
ongeriatry are managed in the context of medical competence sharing.
Main assets for ONCO Lille
C2RC engaged in 2011 a process of actualisation of its medical and scientific project. One of the main axes is the
research: CHRU and COL activities represent a critical mass and a high-powered element for research
development. The project is especially suitable for a site strategy in which both institutions would benefit from
this in terms of lisibility and attractivity.
Elsewhere, the project will integrate the notion of continuum between basic research and clinical research. The
organization is the key of the project: single window, common scientific commitee, standardisation of
procedures, ressource pooling, research professionalisation improved by medical and non medical training
programs linked to the universitiies…The system that C2RC will implement in 2012 will support the SIRIC ONCO
lille project through solid partnerships of the local actors to the benefit of research.
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APPLICATION FILE
Lille Institute of Biology
Management
Pr Y. De Launoit- Director
Contact
 Tel: +33 (0)3 20 87 10 00
 1, rue du professeur Calmette, BP 447, 59021 Lille, France
 http://www.ibl.fr/
Key figures / Key features
In 1996, the "Centre National de la Recherche Scientifique" (CNRS), the French national organization for
scientific research, with strong support of national and regional authorities, created the "Institut de Biologie de
Lille” (IBL) located on campus of the Institut Pasteur de Lille. The IBL research centre was founded to reinforce
basic biology science in the Institut Pasteur de Lille in the Nord-Pas de Calais region by, for example, welcoming
group leaders and permitting them to develop highly competitive research. Research programs were initially
conducted in the fields of human genetic, cellular biology, cancer, microbiology and biomolecule chemistry.
IBL covers a total of 12,000 square meters with about 250 people: Senior scientists, post-docs, PhD and master
students, research assistants and technicians.
It includes 3 mixt research units (UMR 8161, UMR 8199 and UMR 8204) containing:
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55 researchers
118 scientific, technic and administrative staff
13 postdoctorants
44 students
1 start up
In particular, UMR 8161 which is involved in SIRIC programs is composed of:
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20 researchers
24 scientific staff
20 technic and administrative staff
3 postdoc
12 PhD students
4 students
Team involved in ONCO Lille
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Team 1: Cancer Biology and Chemistry (Oleg Melnyk).
Team 2: Functional Analyses of the tumour suppressor gene HIC1 (Dominique Leprince)
Team 3: VE-statin/egfl7 and vascular development (Fabrice Soncin).
Team 4: Initiation of epithelial cancers (Corinne Abbadie).
Team 5: Virus-Cancer-Transcription (Yvan de Launoit).
Team 6: Signalisation, Apoptosis and Cancer (David Tulasne).
SIRIC - CALL FOR APPLICATIONS 2012
APPLICATION FILE
Description (skills & resources)
 The participation of recognized teams in basic research in oncology (more than 200 peer-reviewed scientific
publications between 2006 and 2011, including 12 in journals of IF≥ 10)
 An administrative unit takes in charge the administrative, human resources, financial, technical and
computing network management.
 The pooling of resources allowing the creation of technology platforms
 The creation of inter-disciplinary research programs (chemistry/biology and clinical research/basic research)
 An active scientific policy to strengthen the links between existing teams and to support emerging groups
with monstly seminars in the course of which teams present their works and one yearly meeting.
 Industrial partnerships with the accompaniment of the start-up Innobioships
 A program of scientific activities with national and international seminars aimed at the scientific community
and the journal club aimed at post-docs, PhD students and trainees.
Main assets for ONCO Lille
A strong scientific activity in the field of oncology with various subjects:
 Associated cancers to Hepatitis C Virus and Epstein-Barr virus (hepatocarcinomas, Hodgkin’s lymphoma
(HL), nasopharyngeal carcinomas (NPC) and peripheral T/NK-cell lymphomas.
 Gene control by Erg protein in skeletal development and bone metastases in prostate cancer.
 Molecular mechanisms involved in the initiation of epithelial cell transformation (escape from
programmed cell death that could favour the initial emergence of transformed cells as well as their survival
and growth in the tumour).
 The tyrosine kinase receptor MET and its ligand hepatocyte growth factor/ scatter factor (HGF/SF) and the
deregulation of its signalling during tumours through different approaches (signal transduction of MET,
design of novel cancer strategies targeting the MET tyrosine kinase receptor, proteolytic processing of the
Met receptor and transcriptional regulation induced by ligand-activated Met in development and
tumourigenesis.
 The VE-statin/egfl7 gene which is specifically expressed in endothelial cells: functions and expression
during embryonic development and in various pathological conditions.
Several integrated platforms will be a strong support for development of SIRIC programs:
 A tumour model platform with for objective is to provide animal models (Mouse Embryo development and
Transgenic Models) and mostly cancer models (Tumour graft, Tumour growth evaluation, Metastases
development and evaluation)
 The MICPaL platform with 4 technical trays (photonic microscopy, electronic microscopy, atomic force
microscopy and cytometry).
 The Peptide CSB platform “Peptide Chemistry Systems Biology”
 The innovating start-up “Innobioships” which offers ways to unravel biomolecular interactions between
proteins, antibodies, antigens, receptors, ligands, cells, low-molecular-weight compounds, nutraceuticals
and so on.
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Institut de Recherche sur le Cancer de Lille (IRCL)
Management
Pr Jean Krembel – Director
Contact
Tel: +33 (0)3 20 12 92 20
Place de Verdun 59045 Lille Cedex
http://ircl.org/
Key figures / Key features
The Franco-American Foundation recognized of public utility, referred to as the "Institute for research on cancer
of Lille", was established in 1936 as an independent centre of “fundamental research on cancer”. Located in the
close vicinity of the Faculty of medicine, CHRU and Centre Oscar Lambret, IRCL played a key role in the
development of both basic and clinical cancer research in Lille. Its scientific activity, initially dedicated to
biochemical and biochemical approaches, focused during the last two decades on cancer genomics, cancer cell
biology and anticancer drugs.
IRCL covers a total of 2,500 square meters and hosts about 70 people: senior scientists, clinicians, post-docs,
PhD and master students, research assistants, technicians and administrative staff.
IRCL hosts:
 3 research teams belonging to the Inserm U387/JPARC unit (Jean-Pierre Aubert Centre)
 the administration of the Institute of Predictive Medicine and Therapeutic Research (IMPRT, scientific
director: Régis Bordet, administrative director: Maud Collyn)
 two integrated platforms: the Functional Genomics Platform (IMPRT, University of Lille2 and IRCL - director:
Martin Figeac - IBiSA and EQUIPEX label) and the Cytometry and Cell Sorting Platform (IMPRT - director:
Nathalie Jouy - IBiSA label)
 TuDor Biotech, a start-up created by a researcher from one of the JPARC teams
Team involved in ONCO Lille
 Team 3: Factors of persistence of leukemic cells (Bruno QUESNEL)
 Team 4: Molecular and cellular targeting for the treatment of the cancer (Pierre FORMSTECHER)
Description (skills & resources)
 The participation of recognized teams in basic and clinical research in oncology (86 peer-reviewed scientific
publications in journals of IF>5 between 2006 and 2011, including 30 in journals of IF>10, like NEJM, JCO,
JNCI and Blood)
 Organization of scientific meetings and seminars to strength the links between teams
 An administrative unit takes in charge human resources and financial management.
 IRCL hosts the common warehouse of the Jean-Pierre Aubert Research Centre, providing biological reagents
and cell culture vessels to all teams.
A specific mission of IRCL administration is to stimulate and collect donations from givers. For this purpose, IRCL
has an active communication policy targeting regional media (newspapers and TV networks), organizes various
events open to the public and develops specific contacts with lawyers and notaries to encourage donations
(inheritance).
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Main assets for ONCO Lille
 By providing a stimulating scientific environment for clinical researchers, laboratory surfaces for academic
research teams and key technological platforms, IRCL, ideally located next to CHRU and COL, plays a pivotal
role in the development of translational cancer research on the Lille University medical campus
 A strategic contribution of IRCL is its ability to mobilize money in a very flexible and reactive manner to
support emerging projects, hire post-docs and technicians and accelerate technological evolution, by giving
starting support for buying new equipments.
 By supporting and accelerating the development of an outstanding functional genomics facility dedicated to
cancer research, IRCL gives a selective advantage to its research teams, leading to outstanding scientific
contributions in the field of the molecular characterization of leukaemias.
 Being a foundation, IRCL can mobilize private money. It is the only foundation dedicated to cancer research
in the North of France.
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APPLICATION FILE
Institut Pasteur de Lille
Management
Pr Jacques Richir- Director
Contact
 Tel: +33 (0)3 20 87 78 00
 1 r Prof Calmette 59000 LILLE
 http://www.pasteur-lille.fr/
Key figures / Key features
The Institut Pasteur de Lille is a private non-profit foundation whose mission is to contribute to the prevention
and treatment of diseases through research, training and public health actions. Research and prevention have
always been closely linked. At the origin of the development of the BCG vaccine (Bacille Calmette et Guérin),
the Institut Pasteur de Lille employs today more than 400 people working every day to bring improvement in
the health domain. Internationally recognized medical teams conduct research on the major diseases: cancer;
diabetes; obesity; neurodegenerative diseases, such as Alzheimer's disease; infectious diseases such as
tuberculosis and parasitic diseases such as malaria.
Team involved in ONCO Lille
Y DeLaunoit, J Vicogne, V Fafeur, E Adriaenssens, F Soncin, D Tulasne, O Melnyk, N Delhem, M Duterque, R Bourette
Description (skills & resources)
In addition to research activities, the Institut Pasteur de Lille is a training centre, an international vaccination
centre approved by the World Health Organization and a compelling actor of regional public health: a reference
on all questions about nutrition and the largest centre of health examination to the North of Paris. The Institute
also offers health workshops on food, memory or conditioning to physical effort and consultations to stop
smoking, better manage its consumption of alcohol or take stock of his physical activity.
The Institut Pasteur de Lille Lille hosts several high level Research Units:
 INFECTION AND IMMUNITY with the Centre d'Infection et d'Immunité de Lille [CIIL] (Director: Camille
LOCHT)
 CANCER with the Institut de Biologie de Lille (Director : Yvan de LAUNOIT) and the Laboratory of Toxicology
(Daniel MARZIN)
CARDIOVASCULAR, METABOLIC AND NEURODEGENERATIVE DISEASES (with 3 teams : Public Health and
Molecular Epidemiology of Aging-Related Diseases (Philippe AMOUYEL); Genomics and Metabolic Diseases
(Philippe FROGUEL); Nuclear Receptors, Cardiovascular Diseases and Diabetes (Bart STAELS)
 CROSS-SECTIONAL AND EMERGING with 4 teams: Biostructures and Molecular Drug Discovery (Benoît
DÉPREZ); Inhibition of Nonsense-Mediated mRNA Decay (Fabrice LEJEUNE); Microbiological Safety Unit
(Michèle VIALETTE)
Main assets for ONCO Lille
The Institut Pasteur groups a series of technological platforms accessible to researchers of the centre:
Pletysmography / Functional Investigation of Airway Diseases, Microscopy - Imaging - Cytometry of the Pasteur
Lille Campus (MICPaL) Facility, Surface Plasmon Resonance Platform, Transcriptomics and Applied Genomics
Group (TAG), Nuclear Magnetic Resonance, Animal Unit, High Security Laboratory, Genomic Analysis
Laboratory, High Throughput Genomic Platform (Genoscreen).
The Institut Pasteur will put at disposal of ONCO Lille its infrastructures and resources.
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APPLICATION FILE
Lille 2 University “Law and Health”
Pr Christian Sergheraert – President
Contact
 Tel: +33 (0)3 20 96 43 43
 42, rue Paul Duez 59000 LILLE
 http://www.univ-lille2.fr/
Key figures / Key features
Lille 2 University “Law and Health” is part of the leading European universities. Associated with major national
research organizations, the University has world-class laboratories and researchers. Lille 2 University offers a full
range of training and career opportunities in 4 major poles: Law, Health, Management and Sport, which do the
reputation of the University.
Key figures
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27, 682 students in 2008/2009
90 Student associations
1198 teachers and teacher-researchers
924 engineers, administrative and technical staff
51 laboratories and research teams linked to Inserm, CNRS
More than 200 national diplomas
More than 200 university degrees
17 sites spread over 188 549 m² of built area
4 academic libraries and various partners documentation centres
139,6 millions of Euros of consolidated budget.
Team involved in ONCO Lille
Y DeLaunoit, J Vicogne, V Fafeur, E Adriaenssens, F Soncin, D Tulasne, O Melnyk, N Delhem, M Duterque, R Bourette,
B Quesnel, P Formstecher, A Lansiaux, R Polakowska, I Vanseuningen, M Cheok, N Porchet, C Preudhomme, JF
Gossens, R Millet, P Chavatte, JP Peyrat, MC Copin, JL Lefebvre, D Chevalier, M Hebbar, E Lartigau, JP Triboulet, C
Mariette, N Penel, S Fantoni, P Frimat, D Huglo, S Mordon, L Mortier, L Lemaitre, P Puech, A Villiers, N Reynaert, T
Alam, F Briatte, A Maucourant, A Duhamel
Description (skills & resources)
A High-level scientific research pole:
Research is a critical mission of the University, strongly associated with large organizations such as the Centre
National de Recherche Scientifique (CNRS) and the National Institute of health and medical research (Inserm), and in
close partnership in the field of health, with clinical research. Privileged partner of the CHRU, it has a pole of research
projects common to both institutions. Below is described the means of Lille 2 to develop research projects:
 51 research teams gather 1200 teachers and teacher-researchers and 924 personnel involved in research. Among
them, teachers-researchers share their time between teaching and research or clinical activities.
 2 doctoral schools: one in the field of legal, political, economic and management sciences, the other in biologyhealth.
 4 major areas of research : Life and Heath sciences, Legal, political and social sciences, Sciences of Management,
Sciences of Sports
 2 federal research institutes: IFR 114 (Predictive Medicine and therapeutic Research Institute) and IFR 142
(Molecular and cellular medicine)
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 3 research centres:
- Centre Jean-Pierre Aubert dedicated to the fight against cancer and to neurosciences (Inserm U 837: centre
mixte de recherche Université Lille 2 - Inserm) ;
- Centre d’Infection et d’Immunité de Lille (Inserm U 1019 - CNRS UMR 8204: centre mixte de recherche
Université Lille 2 - Inserm - CNRS - Institut Pasteur de Lille - Université Lille 1) ;
- Centre de recherches Droits et perspectives du droit (EA 4447)
Lille2 is deeply involved in the SIRICprograms since it hosts numerous research teams of the SIRIC in particular in the
scientific and clinical programs “dormance” and “resistance”, in the biology platform and SHS projects (especially
those concerning health law).
Main assets for ONCO Lille
Lille 2 University develops themes of research of excellence and especially in the field of cancer with in close
collaboration with theCancéropôle Nord-Ouest and Génopole de Lille.
Many technical platforms come in support of this advanced research:
 Structural and functional genomics: a platform dedicated to genome analyses and certified by IBiSA. The
platform is deeply committed to cancer research projects and has been involved in many high level publications in
the field.
 A high-tech animal facility : In the field of cancer, several groups are setting up a number of projects (U387, team
3, Bruno Quesnel, U387, team 4, Pierre Formstecher, U837, team 5, Isabelle Van Seuningen).
 Animal imaging models dedicated to the investigation of large animal models
 Imaging capacities : including the Nuclear Medicine Departments and Radiology Departments. The main
objectives of these groups are to identify the best imaging markers for early diagnosis of cancer and to identify
specific tools for post-treatment follow-up.
 Biotherapy platform
 The CRRC Tumour Molecular Biology Platform, setting up to carry out newly-developed molecular tests as part of
the care of cancer patients in the region.
 The Regional Cancer Reference Centre (C2RC) tumour bank with teams from the CHRU (Anatomical pathology
department and haematology laboratory) and from the COL (Anatomical pathology department) with a high level
scientific production (in 2009, 11 publications for Cell library and 7 publications for tissue library).
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APPLICATION FILE
Lille 1 University “Sciences and Technology”
Philippe Rollet- President
Contact
 Tel: +33 (0)3 20 43 43 43
 Cité scientifique 59655 Villeneuve d’Ascq Cedex
 http://www.univ-lille1.fr/
Key figures / Key features
Lille1 University is a multidisciplinary University: Science and technology, engineering, human and social sciences,
economics and management. It draws its strength from its great research potential such as evidenced by
assessments and international rankings and close collaboration with research organizations with 18,000 students
and open collaborations with the economic and social world.
Key figures
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18, 000 students of which 20 % of international students
10, 000 Auditors in continuing education
1, 500 Teacher-Researchers, teachers of the second degree
162 CNRS Researchers
900 AITOS (Administrative, engineers, technicians and service workers)
40 library posts
153 ITA (CNRS, engineers, technicians and Administrative staff)
80 millions of Euros for budget (pay off)
A domain of 110 ha and implantations to Lille (IAE), Sallaumines, Tourcoing, Wimereux (Marin Station)
Team involved in ONCO Lille
H Hondermarck, X LeBourhis, JF Bodart, T Lefebvre, N Prevarskaya, I Fournier, M Salzet, Y DeLaunoit, J Vicogne, V
Fafeur, E Adriaenssens, F Soncin, D Tulasne, O Melnyk, N Delhem, M Duterque, R Bourette
Description (skills & resources)
Lille1University is one of the three universities of the Lille metropolis. It delivers more than 160 national diplomas
in the field of sciences and technology. It is a member of the Lille University (pole de recherché et d’enseignement
supérieur PRES).
Lille 1 university is divided in several Training and research faculty units = UFR : Biology, Chemistry, Geography
and Planning, Computer electronics Electrotechnics automatics (IEEA), Mathematics, Physics, Earth Sciences,
Economic and social Sciences
The UFR of Biology that covers the fields of biochemistry, cellular biology, microbiology, animal physiology and
vegetal physiology:
 provides a scientific, cultural and professional training in the field of biology
 enhances the professional insertion of students coming from its training
 participates to actions of in-service education
 is a meeting point between trainings, structures (lab and technical trays) and the socioeconomic world.
It is also a high-level basic and applied research produced by:
 11 research labs (with 5 labelled CNRS, INSERM or INRA) federated within 2 Institutes :
- l'Institut de Recherche Pluridisciplinaire en Biologie et Biotechnologie (IRPBB / IFR 147)
- l’Institut Pluridisciplinaire de Recherche en Sciences de l'Environnement (IREPSE)
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 1 attached Institute (Institut de Recherche Interdisciplinaire / IRI)
 3 common centres and technological trays (cell imaging, animal facilities)
 1 marine station
It is also a managment unit with central services that allow users to work in good conditions and in synergy.
Main assets for ONCO Lille
Lille 1 university hosts several basic research teams of the SIRIC of which Inserm and CNRS units that are directly
involved in scientific programs or in the Biology platform. Moreover, an IBIsA labellized Proteomic and
glycobiology platform is well-operational with a.common centre of mass spectrometry, a tray of proteomic
Hi_Prot, a tray of glycotechnologies, a plasmonic Surface resonance tray, a RMN and tray of structural
glycobiology and a MALDI Tof Imaging.
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Lille 3 University “Sciences and Technology”
Jean Claude Dupas- Président
Contact
 Pr Véronique Christophe
 Domaine Universitaire du Pont de Bois, BP 60149, 59653 Villeneuve
d'Ascq Cedex
 Email. [email protected]
 http://www.univ-lille3.fr/
Key figures / Key features
Lille 3 University welcomes each year more than 18,000 students, including 1400 students from 107 countries,
and employs nearly 1500 permanent staff. Its research activity and its training offer cover three main areas:
Humanities, human and social sciences, economics and management. Founding member of the "PRES Université Lille Nord de France", Lille 3 University is engaged in an ambitious approach to increase its reach and
its attractiveness, stating its place in the regional landscape and on the international scene. The University
combines the scientific requirement, pedagogical support focused on the success and new digital practices and
an international outreach through scientific networks.
Team involved in ONCO Lille
 EQUIPPE; EA 4018: Economie Quantitative Intégration Politiques Publiques Econométrie (Economy
Quantitative Integration Public Policy Econometrics). Grade A J FONCEL, S DABO, O TORRES
 URECA EA 1059: Unité de Recherche en sciences Cognitives et Affectives (Unit Research on Affectives and
Cognitives Sciences). Grade A, V CHRISTOPHE, P ANTOINE, JL NANDRINO, E FOURNIER
 GERiiCCO EA 4073: Groupe d’Etudes et de Recherche Interdisciplinaire en Information et en Communication
(Interdisciplinary Research and Study Group in Information and Communication). Grade B A LAMY, G
BLANCHARD, S CHAUDIRON
Description (skills & resources)
QUALITY TRAINING FOCUSED ON THE SUCCESS AND RESEARCH
Training offer is available in 32 license and master options. It revolves around 14 units for training and research
and 2 institutes (IUT for Technological University Institute and Training institute for musicians). The University
delivers more than 160 national degrees per year. Teachings are transdisciplinary and relied on the latest
research, on a rich documentary potential (800,000 volumes), on high-performance equipment (visio
Conference, resource centre for language, resource centre for coaching in training, etc.) and accessible digital
services (University Digital "wireless", digital work environment, etc.).
A POLE OF REFERENCE FOR RESEARCH IN HUMANITIES AND SOCIAL SCIENCES
Lille 3 University tends to become a pole of reference in Humanities and social sciences. It promotes a
multidisciplinary research and cooperation policy with basic sciences. At Lille 3, research is organized around 14
laboratories, of which 4 joint research units attached to the CNRS. Workforce highlights the importance of
scientific capacity: 147 professors of universities and assimilated and 370 assistant professors. In 2009, the
quality of research units has been underscored by AERES; 12 of them (on the 16 then existing) have noted A or
A +.
The University strengthens its research activities particularly in behavioural and cognitive psychology,
information and communication sciences, language, education and sociology centred on the individual sciences.
Since 10 years, the University progressively structured an engineering project and valorisation service which
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supports collaborations with the socio-economic world and diffuses into society the laboratory skills. In 2008, 3
laboratories thus obtained the label “Resource Centre for scientific and technological expertise (CREST)” for
their ability to technology transfer. Lille 3 has to this day many contracts, including 16 contracts with the
national research agency and 4 European projects.
Doctoral training to Lille 3 is embarked on an ambitious will of full integration of doctoral students in the
international scientific community. It is divided into 3 doctoral schools, members of the College doctoral of Lille
Nord de France: ED Sciences of man and society (SHS) of which Lille 3 is the carrier, the ED economic Sciences,
social, development and management sciences (SESAM), ED Sciences for the engineer (SPI). With 683 PhDs, ED
SHS is one of two larger doctoral schools of the region in terms of personnel. It was assessed A by AERES in
2009.
The University brings the MESHS (European House of Human and Society sciences), a service and research unit
in partnership with CNRS to structure the regional interdisciplinary research. The laboratories participate
indeed to opened programs with exact sciences research units. This opening is largely supported by the
university that dedicates one third of its budget to these federative projects including projects relative to Health
(cancer, alzheimer, patient and family caring, rehabilitation…).
Main assets for ONCO Lille
Lille 3 University hosts 3 SIRIC laboratories which develop transversal projects with the field of health and more
particularly in cancer with:
 Information and communication sciences (GERIICO lab – Interdisciplinary study and research group in
information and communication)
 Econometry (EQUIPPE lab – quantitative economy integration public policy econometry)
 Human sciences (URECA lab – research unit on affective and cognitive sciences)
Lille3 give to SIRIC teams the innovating technological M-PACE platform (platform for measuring behaviour in
the areas of perception, action, cognition and emotion) and a platform of public Health.
These teams have initiated and wil develop commun projects with the clinical units of the CHRU and COL. A
strong collaboration between clinician and SHS researchers will be maintained in the framework of scientific
programs developed in the SIRIC and in the aspects of knowledge diffusion.
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European Centre for Human and Social Sciences (MESHS)
Management
Pr Fabienne Blaise - Director
Contact




Fabienne Blaise,
+33 (0)3 20 12 58 30
2, rue des Canonniers, 59000 Lille
Mail : [email protected]
Key figures / Key features
The European Centre for Human and Social Sciences (MESHS) was created in January 2008, from the merger of
the IFRESI (Federative Institute of Research on Industrial Economies and Societies) and the Erasmus
International Institute. The MESHS is a research and services entity (USR 3185), under the control of the CNRS
(National Scientific Research Centre) and various higher education establishments of the Nord-Pas de Calais and
Picardie regions, including the 3 universities of Lille. It is part of the national network of Social Sciences Centres
(http://www.msh-reseau.fr/).
The MESHS is a “flagship project” in the framework of the 2007-2013 National/Regional Projects Contract
(CPER)
The MESHS works in cooperation with 30 partner laboratories: 9 university-CNRS research units, 20 university
research teams, welcoming outside participants, and the laboratory of the Lille National School of
Architecture and Landscaping.
As a result of the participation of these laboratories, the MESHS can solidify the strengths of the Region in most
areas of human and social sciences research (HSS), like, among others, anthropology, sociology, economy,
geography, education sciences, Information and Communication sciences, law, or psychology.
Team involved in ONCO Lille
 CRD&P; EA 4487, Centre de recherches Droits et Perspectives du droit (Law and Legal Perspectives Research
Centre) - The four teams within the CRD&P lab were graded A+ or A
 EQUIPPE; EA 4018: Economie Quantitative Intégration Politiques Publiques Econométrie (Economy
Quantitative Integration Public Policy Econometrics). Grade A
 URECA EA 1059: Unité de Recherche en sciences Cognitives et Affectives (Unit Research on Affectives and
Cognitives Sciences). Grade A
 GERiiCCO EA 4073: Groupe d’Etudes et de Recherche Interdisciplinaire en Information et en Communication
(Interdisciplinary Research and Study Group in Information and Communication).
Description (skills & resources)
The MESHS support doctoral studies in their cross-disciplinary dimension, supporting (financially and
logistically) cross-disciplinaary doctoral seminars of the three HSS graduate schools (“Human and Society
Science”, "Legal, Political and Management Sciences", "Economic, social, land use and management Sciences")
and the meetings organised to help with professional insertion of doctoral candidates.
The mission of the MESHS is to support, organise and provide added value to HSS research by removing barriers
and being a relay between laboratories and disciplines, as well as between human and social sciences and socalled "real" sciences. The Centre creates links between HSS laboratories, competitiveness clusters, regional
concentrations of scientific excellence, businesses and local governments.
Its scientific project is built around 3 orientations:
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 1) Health: between individual experiences and social dynamics;
 2) Dynamics and governance of societies;
 3) Texts, objects, interpretation, and argumentation.
MESHS creates, supports, hosts and manages cross-discipline projects concerned by national and international
tenders (ANR, European Union, etc).
Since 2008, MESHS has obtained 58 contracts, for an approximative total amount of € 5,750,000. It hosts
several health-related research projects. Five contracts have been granted in oncology since 2008, funded by
the National Cancer Institute (INCa), National Cancer League, the APAS or the Foundation of France, SanofiAventis, Roche, Pink Ribbon International on the impact of breast cancer on subjective quality of life of young
women and their partner, the overscreening and risk perception in BRCA1/2 hereditary cancer, the physician’s
emotion regulation strategies and announcement of bad news in cancer and on personalised early active
psychosocial accompaniment aimed at facilitating the return to work of women with breast cancer,
psychometric validation of a breast cancer quality of life of young women and their partner. The MESHS also
emits its own calls for projects for cross-disciplinary proposals: "CPER" (National/Regional Projects Contract) for
cross-disciplinary framework projects (€30,000 for projects requiring an operating budget, €100,000 for
projects requiring equipment purchases; 2to 3-year contracts); "seed" projects to help researchers prepare
national and international cross-disciplinary framework projects (€5,000 for one year); "partnership" projects
for projects organised by several laboratories (seminars, workshops), co-financed by the MESHS for €2,000 (for
one year).
Main assets for ONCO Lille
Because it is upstream of research projects and wide-ranging, MESHS will favour collaborations between health
and Social Sciences and Humanities (or SSH). Cancer research will benefit from its experience in terms of setting
up and managing multi-sectoral interdisciplinary projects.
MESHS will also foster, through its own calls for projects, seed projects which will be a first step in the
preparation for national and international competitive calls.
Eventually, one of MESHS’ objectives is to create a health-SSH platform which MESHS ideally aims at turning it
into an interface linking the sphere of health, patients, their associations and the academia. This platform will
aim at bridging the gap between scholars’ transversal issues to further refine the research issues and their
determinants, and better match future research with everyone’s expectations and needs. It will not be about
“monitoring" health research though; it will rather try and make sure it takes into account cross-disciplinary
issues. Scholars in those fields (humanities and social sciences) will use the whole spectrum of concepts,
references, and issues that are particular to their own disciplines to fruitfully confront individual reflections.
MESHS invites foreign researchers and launches initiatives in scientific mediation and knowledge diffusion
(monthly conferences, “SSH in the spring” – a thematic annual series of conferences in the field of humanities
and social sciences, and various thematic scientific events). It also promotes SSH with events intended for local
authorities and the corporate/business sectors in order for all social stakeholders to acquire a better grasp of
the essential role SSH play in their decision-making processes and actions.
SIRIC will clearly directly benefit from these proactive initiatives.
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“Lille Nord de France University - Research and Higher Education Cluster”
(named PRES-ULNF for Pôle de recherche et d’Enseignement-Université Lille Nord de
France)
Management
Pr Christian Sergheraert – President
Contact
 Anne de Lamotte Tél.: +33 (0)3 20 29 93 82
 1bis rue Georges Lefèvre -F- 59044 Lille cedex
 http://www.univ-lille-nord-de-france.fr/
Key figures / Key features




17 higher education institutions (Universities and high schools)
130, 000 students, 4, 600 researchers and research fellows
3, 000 doctoral students in 6 doctoral schools
200 laboratories of public research with about 2/3 tiers ranked A+ and A by AERES and associated to national
research organizations.
PRES-UNLF focuses largely on public research in the Nord-Pas de Calais region. It also supports the academic
community to work in close collaboration with national research organisations and business and technologic
clusters. All of its activities lead to development of the regional research and higher education.
Team involved in ONCO Lille
H Hondermarck, X LeBourhis, JF Bodart, T Lefebvre, N Prevarskaya, I Fournier, M Salzet, Y DeLaunoit, J Vicogne, V
Fafeur, E Adriaenssens, F Soncin, D Tulasne, O Melnyk, N Delhem, M Duterque, R Bourette, B Quesnel, P
Formstecher, A Lansiaux, R Polakowska, I Vanseuningen, M Cheok, N Porchet, C Preudhomme, JF Gossens, R
Millet, P Chavatte, JP Peyrat, MC Copin, JL Lefebvre, D Chevalier, M Hebbar, E Lartigau, JP Triboulet, C Mariette, N
Penel, S Fantoni, P Frimat, D Huglo, S Mordon, L Mortier, L Lemaitre, P Puech, A Villiers, N Reynaert, T Alam, F
Briatte, A Maucourant, A Duhamel, J Foncel, JL Nandrino, V Christophe, P Antoine, A Mignon, S Chaudiron, G
Blanchart.
Description (skills & resources)
PRES-ULNF was founded in January 2009 in order to increase the regional academic potential, promote its
visibility and enhance its international standing.
It implements a plan of resource pooling of which:
 a common project engineering to answer to national or european calls for proposal
 a policy of purchase and maintenance of high shared equipments
 a common scientific documentation
 a cooperation and project strategy allowing a synergy around thematics able to federate institutions.
It is in charge of coordinate the whole of regional answers to calls for proposal linked to the Plan “Investissements
d’Avenir”.
The PRES-ULNF has decided to gather the existing development structures in a “SATT” (Acceleration of
Technology Transfer Company), a private company named “Nord de France Valo”. This new structure is being set
up in association with the University of Picardie Jules Vernes (UPJV, Amiens), the University Reims Champagne
Ardennes (URCA, Reims) and the CNRS. It is a valorization platformarticulated around several domains:biology
and heath, agricultural sciences, chemistry and materials, information technologies and engineering sciences, and
human and social sciences.
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Main assets for ONCO Lille
Valorisation, transfer and Partnerships
For the health domain a specific department will be part of the SATT This department will gather complementary
skills (scientific, business, legal and IP).The SATT activities will address in particular raising awareness, detection,
maturation, protection and management of the intellectual property, business engineering,contracts, incubation,
technology transfer, and project management.
The SATT, as a unique service centre for researchers and companies, will become a privileged interlocutor for the
competitiveness clusters in terms of identification of innovative projects and collaborative partnerships.
Considering the research areas of the future SATT, the PRES-ULNF gathered with companies and research
laboratories of our inter-regional area to develop synergy and cooperation through eight competitiveness clusters
andin the health domain, aprivileged partnership with the competitiveness cluster NSL(Nutrition, Health,
Longevity) will be established.
The SATTwill constitute an important structure to support technologytransfer and valorization of the SIRIC
scientific programs results.
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ONCOVET
Management
Dr Dominique TIERNY
Contact
Dr D. TIERNY
Tel: +33 (0)3 20 34 41 34
 Immeuble ONCOVET, Avenue Paul Langevin, 59650 Villeneuve d’Ascq
http://www.oncovet.net
Key figures / Key features
Oncovet is a private veterinary referral centre located on campus of “cité scientifique” Villeneuve d’Ascq
(North, France) and dedicated to diagnostic, imaging and treatment of spontaneous cancer in dogs and cats.
Oncovet has 11 years’ experience in these specialized activities and works with a regional international
network of over 1000 veterinary practitioners in France and in the Benelux countries.
Oncovet occupies a total surface of 1200 square meters with about 25 people. The team consists in 10 clinicians
and several nurses offering surgical and cancer treatment facilities. Practitioners are dedicated to their own
field of activity: internal medicine, medical oncology, diagnostic imaging (ultrasound, CT-Scanning,
scintigraphy), surgery, chemotherapy and radiation therapy.
Team involved in ONCO Lille
D. Tierny, A. Hidalgo, F. Serres, L. Marescaux, C. Robat, N. Granger, H.Brissot, Elsa Edery, M.Pottier, E.Cathelain
Description (skills & resources)
Most of the Oncovet clinicians had academic, clinical or teaching experience before entering the group and
have a further university diploma in their specialist field. Most have collaborated with institutional medical
research groups before (CNRS, Inserm). The clinicians have published over 25 referenced papers altogether in
their fields and numerous articles in the French veterinary professional literature. Several veterinary theses
have been written on the various internal oncology surveys. Oncovet has been working with different
pharmaceutical companies and academic laboratories for clinical or preclinical research in the field of oncology
for several years.
Based on the caseload in small animal, the technical platform and the specialization of the senior scientists,
Oncovet will provide individual training programs of residency to specialize in veterinary diagnostic imaging,
surgery, oncology and neurology.
The technical platform available at Oncovet is among the most highly developed in veterinary medicine in
France :
Radiography
 SMAM Easymobil M32
 KONICA Regius 110 (digitization and workstation)
 GE Stenoscop (fluoroscopy)
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Ultrasonography:
 ESAOTE MyLab 60 (transducers : convex 1-8 MHz contrast compatible, microconvex 3.5 -9 MHz, linear 6-18
MHz, phased array 1-3.5 MHz, phased-array 3.5-5 MHz)
Computed tomography:
 SIEMENS Somatom Spirit
Nuclear medicine:
 SIEMENS ECam
Radiation therapy:
 PANTAK DXT300 (orthovoltage radiotherapy)
 NUCLETRON Microselectron (brachytherapy HDR)
 ONCENTRA (workstation for dosimetry)
Two surgery rooms, equipied for interventional catheterism
Four animal housing
Clinical laboratory: complete blood work, biochemistry, coagulation profile
Hemodialysis Unit (HEMOTECH)
Main assets for ONCO Lille
A specialist referral oncology veterinary centre
 A continuous flow of patient with spontaneous tumours, evaluated treated and followed up according to
standardized protocols (2000 newly diagnosed patient each year).
Our expertise field
 Oncology, diagnostic imaging, internal medicine, cardiology, neurology, surgery, hospitalization, clinical
pathology, and histopathology
Our technical installation
 Scanner, echography, scintigraphy, numeric radiography, fluoroscopy, endoscopy, orthovoltage
radiotherapy, HDR brachytherapy, surgical installation, chemotherapy, hospitalization, laboratory of clinical
pathology, histopathology and immuno-histochemistry on site
Our team
 10 specialists veterinarians
 12 veterinary nurses, 2 medical secretaries, 1 clinical research responsible, 1 quality responsible
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I.3. Strategic considerations for ONCO Lille
I.3.1. A RESPONSIBILITY, A VISION AND AN AMBITION
Being the region with the highest cancer incidence in France, our responsibility is to be able to
make a definitive breakthrough in the understanding of two of the most significant biological
and clinical issues in modern oncology: tumour and host resistance to loco-regional treatments
and the role of tumour dormancy/persistence in clinical relapse.
We have seen that currently the number of new cancer cases In France was every year > to
300,000 with an increase in an 89% increase in incidence since 1980. Demographic changes
(increase of the general population and aging) have been responsible for almost half of that
increase and the remainder has been largely explained by increases of breast and prostate
cancer
incidence
through
screening
and
early
diagnosis
(http://www.invs.sante.fr/surveillance/cancers/estimations cancers/default.htm).
Between 1980 and 2005, the increase of cancer-related deaths (12%) was due to demographic
changes, but the mortality risk rate decreased during the same period of time (-2.5% [men] and 1.2% [women] last 5 years). This divergence in cancer incidence and mortality trends in France
over the last two-decade period can be explained by the combined effects of a decrease in
the incidence in some aggressive cancers (stomach, lung in men) as well as changes in medical
practices leading to earlier diagnoses and better care.
When referring to data obtained by various departmental French cancer registries the Nord –
Pas de Calais region displays the highest rate of cancer incidence and cancer mortality in
France and one of the highest in Europe (http://globocan.iarc.fr/).
For example, the over-incidence of hepatocarcinoma (HCC) is 40% (male) and 70% (female)
higher in the Nord – Pas de Calais region than in France.
When
comparing
the
standardized
rates
in
France
and
our
region
(http://www.orsnpdc.org/donnees/territoire.html), the mortality linked to oral cancers (mouth –
lips – pharynx) in Men is 84% higher than in the other regions of France; this rate being one of the
highest in the World. For oesophageal cancer, the mortality rate is roughly 75% higher in this
region than in the rest of France (Men 83.8% and Women 58.4% in 2004-2007).
Over the past years, social inequalities have been pointed out as an important parameter
explaining the over-incidence of cancers in certain regions of France. This phenomenon has
been exemplified by deaths linked to head and neck and oesophageal cancers in Men, which
are respectively 4.4 and 5.2 times higher in the less-educated population than in the welleducated one (Menvielle G, Leclerc A, Chastang JF, Luce D. Inégalités sociales de mortalité par
cancer en France : état des lieux et évolution temporelle. Bull Epidemiol Hebd. 2008;33:289-92.).
Cancer deaths linked to social differences are mainly due to social inequalities of cancer
incidence as well as cancer care. In the Nord–Pas de Calais region, this phenomenon is
amplified but the risk factors associated to these cancers (smoking, alcohol, oral hygiene, HPV
infection, educational and socio-economical levels…) do not fully explain all this over-incidence
and over-mortality of preventable cancers. It is of great interest to better understand the co
existing risk factors and their impact on over-incidence, over-mortality and survival in these
cancers.
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Men
Nb of
cases
in CLA
Women
Standard
Incidenc
e Rate in
CLA*
Standard
Incidence
Rate in
France*
CLA/
France
Ratio
Nb of
cases in
CLA
Standard
Incidence
Rate in
CLA*
Standard
Incidence
Rate in
France*
CLA/
France
Ratio
Head & Neck
198
46.5
21.8
2.1
37
6.9
5.2
1.3
Oesophagus
64
14.4
7.9
1.8
14
2.0
1.5
1.3
224
47.7
37.7
1.3
209
30.2
24.5
1.2
Liver
64
14.3
10.4
1.4
27
3.4
2.0
1.7
Larynx
44
9.5
7.1
1.3
5
0.7
1.0
0.7
320
70.9
50.5
1.4
75
13.2
12.6
1.0
6
1.1
1.2
1.0
4
0.4
0.4
1.0
35
6.9
7.6
0.9
32
5.3
8.8
0.6
645
139.2
121.2
1.1
Uterus
79
13.9
10.0
1.4
Ovary
68
12.3
8.1
1.5
Colon rectum
Lung
Pleura
Melanoma
Prostate
Rate for 100 000 inhabitants per year standardized for the world population
**Belot et al., Cancer incidence and mortality in France over the period 1980-2005, Revue d’Epidémiologie et de Santé Publique 56(2008) 159175
CLA = City of Lille area
ONCO Lille can drive the leading oncology program in an area covering North West of France
with the Cancéropôle Nord-Ouest (see chapter IV) and part of Champagne Ardennes (Reims),
representing around 12 million inhabitants (1/5 of the global French population), area
characterized by a very high cancer incidence (see following map).
In addition to the epidemiological data which clearly indicate over-incidence and overmortality of these preventable cancers in the Nord–Pas de Calais region, the proposed research
axes are directly supported by a strong expertise in clinical and basic research.
Due to these considerations, the scientific, medical and political community of Lille and its region
strongly believe that the reinforcement of existing collaborations could be very successful to
bring new models and new explicative pathways in the field of oncology.
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Nord Pas- de- Calais
Cancer Mortality in France, 2004 - 2007
In 2010, Lille competed to the SIRIC tender but was not granted. The comments and
recommendations of the reviewers at the time have been integrated for the 2011 answer.
Based on our specific cancer incidence, the 2010 program was focusing on the concept of
preventable cancers and recurrences. The limits in our 2010 organization have been totally
considered in order to present a much stronger answer around fundamental and clinical
research. However the social and clinical reality of our cancer incidence remains and the
integration of human sciences is still strong in our 2011 project, together with fundamental and
applied research projects.
For these reasons, the medical and scientific community is particularly ready in 2011 to answer
to the INCa tender, our program being totally, and even more, integrated in the framework of
Plan Cancer 2 (2009-2013).
ONCO Lille has the legitimacy to develop an original project aims to achieve state of the art
integrated research in some of the most important issues for oncology: tumour resistance and
persistence after loco-regional treatments. Based on a large number of clinical and
fundamental research programs in aggressive diseases (oesophagus, liver, melanoma, head &
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neck...) or most common diseases (prostate, gynaecology, haematology…), and on the existing
level of excellence, the 2 integrated programs are:
Program 1: tumour and host resistance to loco regional treatments in the field of head and
neck, oesophagus, liver and gynaecological tumours.
Program 2: tumour dormancy and persistence in the field of haematology, melanoma and
prostate cancer.
With the support of the partners from Political institutions (Regional Council) and the University of
Lille-Nord de France, our vision is through ONCO Lille to develop 2 global research programs
supported by 4 integrated platforms.
With this project, we will reinforce the existing synergy between the research in human, social
and life sciences. Moreover, the direct interface with the clinical research units will be crucial in
the present research project.
For example, the vast majority of oesophageal cancers seen in the Nord-Pas de Calais region is
directly addressed by physicians to the surgical department of the University Hospital of Lille (Pr
Mariette and Pr Triboulet) or to the oncology department of the cancer centre (Pr Adenis and Dr
Mirabel) that are responsible for (i) extension diagnosis, (ii) multidisciplinary therapeutic strategy
and (iii) inclusion in clinical trials. This large active patients‟ file is a unique opportunity for studying
such population. The physicians involved are recognized international leaders.
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Targeting the biological
mechanisms at the basis of
cancer resistance and
dormancy
A comprehensive
research strategy from
basic science to the
patients benefit
A global and innovative
approach
to cancer care
Developing innovative
therapies
targeting resistance and
dormancy
With ONCO Lille, the integration of all disciplines in globally integrated programs is a reality.
The impact of the 2 programs will be very significant in the comprehension of biological
mechanisms of tumour dormancy, persistence and resistance to treatments and will drive
treatment recommendations directed to the benefit of the patients together with impact on
access to care and formalized follow up and reinsertion actions.
They have the originality to stand on very strong basic or clinical research and to be able to
achieve significant breakthroughs in the modelling of resistance to initial treatment and
recurrence after treatment for the benefit of patients and healthcare providers.
Our ambition is to be at term a European leader in these fields, driving innovative research,
implementing new clinical research with up to date evaluation and modern knowledge
dissemination.
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I.3.2. THE RESEARCH FACILITIES
All the research facilities are fully described in part II. The ONCO Lille Consortium gathers
outstanding strengths of researchers in basic, translational and clinical research (labelled A+ and
A teams) with very successful developments (genomic, proteomic, tumour bank, animal models,
imaging, methodology...).
However, we must insist on the capacity of ONCO Lille to develop all the requested resources in
the field of our projects, from basic sciences to human sciences through imaging & animal
facilities, international clinical research and reference methodological evaluation.
As stated above, our tumour bank has been considered at the 2009 evaluation to be the one
with the highest scientific value in France (see platform 1).
Our imaging facilities cover all scopes from molecular to therapeutic tools with very
innovative research in the field of Mass Spectrometry Imaging (MSI) (see platform 2).
Our animal facilities cover all needed models with the originality of Oncovet. This veterinary
clinic is the only one in France specifically devoted to animal oncology. It brings specific
spontaneous tumour models which will be very valuable in program 2.
The methodology teams of the CHRU and the Col have been at the forefront of clinical
research evaluation. All clinical research is evaluated and granted at the national level by
using tools (SIGAPS www.sigaps.fr, SIGREC www.cengeps.fr/Logiciel-SIGREC) developed in Lille
(see platform Methodology and clinical research).
Furthermore, the human sciences are a particularity of Lille with the daily interaction between
HS researchers and clinicians in the field of oncology (see program 1)
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This original approach of bringing together the research facilities around 4 platforms, under the
supervision of a single pilot, will help a lot for the coordination and the success of our programs.
I.3.3. TOWARD AN INTEGRATED RESEARCH CENTRE
When answering to the INCa tender, the notion of integration is a key factor for the evaluation.
ONCO Lille is the archetype of such integration, bringing together academic institutions with a
past history of multidisciplinary collaboration, research facilities around shared platforms, large
research programs very well focused on important medical questions with a strong interaction
with human sciences.
Part of our legitimacy is based on the capacity to bring all fields of oncology together around
pathologies which are very frequent in our medical surrounding: haematology, oesophagus,
head and neck, mesothelioma, liver, prostate. All programs will integrate biological research,
translational research, innovative imaging, clinical research and humans sciences
developments, particularly in the field of comprehensive handling of the disease for the patient
and the family (global care).
To be successful, such a program must have a strong coordination, interactions with external
cooperations, industrial partnership and valorisation, and must serve the population and the
colleagues by a teaching policy. All these aspects are covered in our project and are
synthesised in the figure and developed in the various chapters.
ONCO Lille will have the opportunity to achieve the scientific goals but furthermore, by getting
the SIRIC label, to develop its attractivity to bring young researchers in the field of Oncology.
Management and organisation – E. Lartigau
INTEGRATED RESEARCH PROJECT
Program 1
National and
international
collaborations
program
Resistance
C. Mariette
Program 2
Human and Social
Sciences
V. Christophe
Dormancy
B. Quesnel
Platforms
P. Formstecher
Biology
Imaging
Animal
models
Y. De
Launoit
I. Fournier
D. Tierny
Clinical
research and
methodology
A. Duhamel
Knowledge and practices dissemination program – S Fantoni
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Industrial
Partnerships &
valorisation
program
SATT –
Eurasanté
A. Coilliot
APPLICATION FILE
I.3.4. MANAGEMENT AND ORGANIZATION OF THE SIRIC SCIENTIFIC ISSUES
The global management of ONCO Lille is described in following sessions. The main issue for us is
the capacity to reinforce our already existing collaboration in order to develop the attractivity of
our scientific and medical community.
Based on the excellence of the research platforms and of the clinical research/methodology
actors, the principle of ONCO Lille management will be to reinforce the interaction by bringing
new researchers in the field of integrated research in Oncology. Due to the deep involvement of
the political community (Regional Council, Urban Community...), research in Oncology is already
considered as a priority and getting the INCa SIRIC label will help us strongly to gain in
attractivity.
The role of ONCO Lille management will be to continuously support emerging projects, develop
exchanges on the ongoing projects, develop new approaches or initiatives, enhance
valorisation and finally to disseminate through education.
Through our scientific steering committee and with the help of our international scientific
committee, ONCO Lille will promote its research results at the European and International level.
I.3.5. CONTRIBUTION TO THE OBJECTIVES OF THE PLAN CANCER II
The strategy behind the plan cancer is based on three major cross-cutting themes. These are the
primary focus of the plan and are found in every area, expressed as specific measures and
actions:
take more effective account of health inequalities to ensure greater fairness and
effectiveness in all the measures taken to fight cancer;
encourage analysis and taking account of individual and environmental factors to
individualise patient care before, during and after their illness;
strengthen the role of the referring doctor at every stage in the patient‟s treatment, in
particular to improve quality of life during and after their illness.
This is reinforced by 6 “flagship” measures:
Measure 1 Increase resources for multidisciplinary research, by accrediting five multidisciplinary
cancer research integrated sites
Measure 3 Define environmental and behavioural risks.
Measure 6 Produce and communicate information on cancer and cancer research and
treatment.
Measure 14 Tackle inequalities in access and take-up of screening.
Measure 18 Individualise patient care and expand the role of the referring doctor
Measure 25 Develop individualised social support during and after cancer. This plan will take
account of individual needs in terms of medical supervision and psychological and social
support.
All these issues are clearly addressed in ONCO Lille programs.
I.3.6. INTERNATIONAL COLLABORATIONS
Cooperations have been already developed with local and regional biotech companies‟
trough the Eurasanté Incubator. Furthermore the existing regional (Cancéropôle Nord Ouest)
and international (Belgium, Netherlands ...) cooperations will be strongly reinforced.
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I.3.7. VALORISATION STRATEGY
The overall objective of the valorisation strategy will be to ensure ONCO LILLE as a leading
European Oncology centre over the next five years.
To meet this priority, the following key strategic actions will therefore be:
1. To transform research investment in IP
2. To develop of an effective partnership strategy with industry
- By reinforcing numerous existing partnerships,
- By developing new and fruitful partnerships
3. To develop a communication strategy that will enhance the attractiveness of ONCO Lille
In order to reach these goals, the technology transfer organization will be implemented in
partnership with the future SATT Nord de France Valo and Eurasanté. EuraSanté and the
members of the future SATT Nord de France Valo have a proven track record in the field of
technology transfer, particularly in health and biotechnologies (see chapter V for examples of
technology transfer successes in both PME and start up).
These bodies will have a clear assignment, aiming to boost the technology transfer, the
economic added value and the attractiveness of Onco Lille.
I.3.8. DISSEMINATION STRATEGY
Dissemination of knowledge will be directed towards patients in the field of adapted follow up
and professional reinsertion, as well as towards general practitioners (referring doctor) and
political authorities. Trough a close collaboration with the faculty of medicine & the faculty of
pharmacy and biological sciences, the most valuable results will be integrated in teaching
(masters).
I.3.9. CONCLUSION
The two integrated programs developed by ONCO Lille, on the backbone of 4 state of the art
integrated platforms combined with Human Sciences resources, will have the capacity to put all
research forces in very close interactions.
The reactivity of our research groups has been already demonstrated through the national
evaluation of our Tumour Library or the participation of the Lille research team within the Nord
Ouest Cancéropôle.
As the history of collaboration and integration is already strong (C2RC) in Lille and due to the
very high incidence of cancer in our Region, the INCa/SIRIC label will be given to a scientific and
medical organization able to challenge europan comparable comprehensive cancer centres.
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II.
Presentation
of
the
medical,
scientific
technological potential of the SIRIC
and
II.1. Medical activity
II.1.1. CHRU LILLE
The Centre Hospitalier Regional et Universitaire de Lille (CHRU) is the only University Hospital of the
Nord-Pas de Calais region (4 million inhabitants) and is the regional reference platform for most
medical, surgical and technical activities (imaging, biology, functional explorations, information
system).
Developing new technologies, promoting research and training professionals, the CHRU of Lille
has 2 965 beds (1091 in medicine, 868 in surgery, 231 in Gynaecology-obstetrics, 228 in long-term
care, 148 in Psychiatry … ) with the expertise of 13.500 employees (including 3000 physicians).
It plays a major role in the permanence of care including the emergency units with 120,000
passages, each year. In 2010, the CHRU de Lille hospitalized 93 671 patients and realized 1,192
290 consults, 5 200 births took place, and it registered 950 publications in scientific journals, and
9000 medical students were supervised.
Responding to his missions in care, innovation & research and teaching & training, the CHRU de
Lille allows equal access of patients to high-tech care networks through platforms in imaging (6
MRI‟s including 1 dedicated to research, 12 CT scanners, 7 digital angiographies, 7 gamma
cameras, 1 positron Emission tomography), surgery (80 operating rooms, 1 surgical robot, 114
resuscitation beds and 95 beds of continuous monitoring) and others : 3 equipment for
extracorporeal circulation, 59 renal dialysis posts, 16 surgical lasers, 1 Stereotactic radio-surgery
(Gamma-Knife ®). One biology pathology Centre has been open in 2009 including 23
laboratories with common molecular biology and cell culture, dealing with 10 000 samples per
day.
The CHRU de Lille‟s activity represents 11% of the regional activity. It is the reference care centre
for all the inhabitants of the Nord Pas de Calais Region (in 2010, 39% of stays concerned people
who came from the entire region, outside the urban area of Lille) and also provides the role of
"proximity" to the inhabitants of its territory health.
The Academic Hospital has a yearly budget of 950 millions €.
The expertise of multidisciplinary teams of CHRU de Lille, which was recognized by the
certification of reference centres and skills centres, is based on medico-technical platforms and
accommodations continuously upgraded through a policy of sustained investment: the CHRU
annually invests around 50 million Euros. This effort was brought to 67 million Euros in 2010 for the
launch of the implementation of "Project South," restructuring project of the South campus
university hospital.
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II.1.1.1. ORGANIZATION OF CANCER TREATMENT AT THE CHRU
The coordination of the oncology activities is ensured by the "Federation of Oncology ", which
constitutes an internal network support.
For each tumour localization, a multidisciplinary Committee of oncologists, pathologists,
physicians, surgeons, radiologists, radiation therapists is organized. Every Committee is primarily
responsible for defining the diagnostic and therapeutic strategies. More than 150 senior
practitioners participate in these committees, articulated around the following clinical situations:
Skin,
Digestive Oncology (two sub-committees according to locations: liver/other locations),
Endocrinology,
Gynaecology and breast,
Haematology (four sub-committees: leukaemia, lymphoma, myeloma and transplants),
Bone metastases,
Neuro-oncology,
Onco-Paediatrics,
Thoracic Oncology,
Urology,
Head and Neck and Eyes.
The Federation provides support, and especially medical psychology care coordination and
liaison psychiatry (5 onco psychologists), patient education (stoma therapy, smoking and
physical activity in connection with the Lille University Club), re-education - rehabilitation,
nutrition, support for the pain, sexual disorders and fertility (including Ovarian conservation),
social support and palliative care.
The “Centre de Coordination en Cancérologie”, also known as 3 C guarantees the quality of the
response to the different procedures for certification or accreditation ensures security of
chemotherapy with Pharmacy and organizes the 26 annual training policies. It also coordinates
medical secretariats of Oncology, manages the statistical database of multidisciplinary
meetings, ensures the annual audit of the activities of the Federation.
Patients‟ information Areas, “AIR cancers”, are specific sites delivering all general information on
the disease prevention and treatment. “AIR cancers” also offers cultural activities in liaison with
the media library of Lille University Hospital and with external partners (Museums).
The Federation promotes patient support and encourages the emergence of innovative
activities and scientific projects in the field of malignancies, and in particular the collaborations
with Northwest Cancéropôle fundamental research units and laboratories. The Federation of
Oncology from CHRU participates in connection with the Faculty of medicine - including its
continuous medical education Department and Centre Oscar Lambret - to theoretical and
practical teaching as well as continuing education for physicians, medical students and staff.
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II.1.1.2. CANCER TREATMENT
The CHRU de Lille is the first institution within the north west interregion for cancer patients with
9 976 in-patients hospitalized in 2010 (95% of adults and 5% of children).
On that scale, cancer patients represent 10% of all in-patients of the CHRU, and they also
represent 16.2% of hospital stays of the CHRU corresponding to 29 251 stays in year 2010.
The number of patients treated for cancer at Lille University Hospital has increased by 16.7%
since 2005 (see below). 70% to 75% of these patients are new oncology patients.
2005
Nombre de séjours
Nombre
total CHRU Lille
Nombrededeséjours
séjours
Nombre de séjours avec un code de cancer
Nombre de séjours total CHRU Lille
évolution / N-1
Nombre de séjours avec un code de cancer
évolution / N-1
Nombre de patients (Adultes + Enfants)
Nombre
total(Adultes
CHRU Lille +(source
DIM)
Nombrededepatients
patients
Enfants)
Nombre de patients avec un code de cancer
Nombre de patients total CHRU Lille (source DIM)
évolution / N-1
Nombre de patients avec un code de cancer
* NBévolution
: données/ N-1
patients 2005 et 2006 = ONCODIM
2006
2007
2008
2009
2010
nb
%
nb
%
nb
%
nb
%
nb
%
nb
%
nb
%
nb
%
nb
%
nb
%
nb
%
nb
%
2005
2006
2007
2008
2009
2010
157nb547 %
165nb878 %
164nb660 % 172nb256 % 178nb012 % 180nb884 %
25 507 16,2% 26 509 16,0% 26 449 16,1% 26 979 15,7% 28 332 15,9% 29 251 16,2%
157 547
165 878
164 660
172 256
178 012
180 884
-0,2%
2,0%
5,0%
3,2%
3,9%
25 507 16,2% 26 509 16,0% 26 449 16,1% 26 979 15,7% 28 332 15,9% 29 251 16,2%
-0,2%
2,0%
5,0%
3,2%
3,9%
2005*
2006*
2007
2008
2009
2010
2005*
84nb300 %
8 542 10,1%
84 300
8 542 10,1%
2006*
88nb458 %
8 701 9,8%
88 458
1,9%
8 701 9,8%
1,9%
2007
91nb140 %
9 072 10,0%
91 140
4,3%
9 072 10,0%
4,3%
2008
92nb966 %
9 302 10,0%
92 966
2,5%
9 302 10,0%
2,5%
2009
93nb671 %
9 650 10,3%
93 671
3,7%
9 650 10,3%
3,7%
2010
93nb483 %
9 976 10,7%
93 483
3,4%
9 976 10,7%
3,4%
* NB : données patients 2005 et 2006 = ONCODIM
Patients are mostly treated for digestive cancer, haematology, respiratory system cancer and
metastatic locations.
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II.1.2. CENTRE OSCAR LAMBRET
The COL is the regional reference cancer centre. As an academic hospital, it is only dedicated
to care, research and teaching in the field of Oncology. The COL employs 780 professionals,
including 96 doctors and scientists for a global budget of approximately 80 million Euros in 2009.
Patient care is organized around multidisciplinary services, including surgical, medical and
radiation oncologists. This organization, unique in France, guarantees that all aspects of cancer
treatment are taken into consideration at one time.
This expertise is maintained at a level of excellence by an ambitious professional training plan
developed each year in consultation with Department Chairmen and managers of all logistical
and administrative sectors.
Every day, more than 100 health professionals are entering the Centre for training (students,
junior doctors, engineers, biologists, students from para-medical schools …). Since 2008, the
Oscar Lambret Formation Institute (IFOL), certified by the 3 national colleges of the continuous
medical education, offers a catalogue of training themes. In 2010, training effort supported by
the COL exceeded 1.7 million € for 780 employees.
Certified in 2005 and 2009 by Haute Autorité de Santé, the COL has been classified first of the 20
cancer centres for quality of care and patient satisfaction in a survey conducted in 2009 by the
Fédération Nationale des Centres de lutte contre le Cancer (FNCLCC).
The medical imaging and radiation oncology platforms have been totally modernized (2 CT
scanners, a 3T MRI, a PET CT, 1 CyberKnife, 2 Tomotherapy, 3 Linacs).
The COL provides access to innovative diagnostic and therapeutic techniques, particularly in
the following areas: surgery, oncogenetics, radiotherapy, imaging, brachytherapy, pathology
and molecular biology, supportive care and pharmacology. The COL has since 2003 a
Paediatric Oncology unit that supports the entire solid tumours of the children from Nord-Pas de
Calais in association with the CHRU, and a pilot unit in aging patients. Most of the activities are
labelled by the INCa.
The COL has produced in 2009: 37,000 conventional days of hospitalization, 49 000 annual
consultations, 4500 surgical acts, 50,000 radiation sessions, 20,000 out-patient chemotherapy
treatments. 5 864 patients have been treated in 2010 at the COL.
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The research activities are under the authority of the Director of research, Prof. Eric Lartigau and
subject to a regular evaluation by an external Scientific Council chaired by Professor Jacques
Robert (Bordeaux). The COL develops research activities at the interface of basic research and
highly specialized care (genetic testing, cellular targeting) and in integrated clinical research.
An internal 27 review committee (Committee of clinical studies -CEC), meeting every month,
investigates and selects all projects submitted for clinical research. Laboratory research is held in
the laboratory of Dr. Amélie Lansiaux, MCU - PH at the Faculty of Medicine Henri Warembourg in
anticancer Pharmacology and in the laboratory of Prof. Jean Philippe Peyrat in human
Molecular Oncology.
The Clinical research integrated unit (UIRC, see appendices) has an intense promotional activity
that put the COL, in 2009, in the second position of the 20 CLCC (data FNCLCC 2010) with over
50% of the total PHRC selected in the Cancéropôle Nord-Ouest in the past 3 years. With more
than 10% of his patients included each year in an interventional study, the COL is part of the rare
health institutions to have exceeded the goal in clinical cancer defined in plan cancer
At the regional level, the 3 cancer Centre of Lille, Caen and Rouen cooperate between within
the framework of the "C cube" as an interregional platform in clinical research labelled by the
League, which hosting the data Centre for Clinical Research (CTD INCa).
Past 5 years achievements at the COL:
2006: Coordination of supportive care. This action is following the definition of supportive care
made in 2004 by the health authorities and as also present in the 2003-2007 plan cancer 1.
2007: Opening of the clinical research integrated unit equipped with 4 rooms to
accommodate patients included in early phase (I, early II) clinical studies. Deployment of
PACS (Picture Archiving and communication system). 14 June 2007: first patient treated with
CyberKnife ®.
2008: 20 June 2008: inauguration of the Da Vinci Surgical robot. Development of the
brachytherapy unit. First French centre in the number of treated patients, Centre Oscar
Lambret has improved in July 2008 its equipment brachytherapy for the comfort of the
patients. Dedicated radiotherapy simulation CT (90 cm)
2009: Creation of the Training Institute Oscar Lambret (IFOL) TomoTherapy machines January
and May 2009).
2010: opening of the 3T MRI.
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II.2. Research activity
II.2.1. FUNDAMENTAL SCIENCES
II.2.1.1. BIOLOGY
ONCO Lille combines biology research groups from CNRS & INSERM) as well as Universities (Lille 1,
and 2, PRES). Most of the research activities are labelled at the national or international level
(AERES, AICR, ligue contre le cancer, ARC, INCa, région NPC…). Research activities on cancer
are already strongly structured. In fact, scientific, academic and hospital institutions are joined in
a Committee of biomedical research and public health to define four priority areas: Cardiovascular and metabolic - Inflammation and Immunology - Neurosciences - Cancer. This research
is carried out on three different geographic sites: the CHRU site, where research teams are in
close interaction with the hospital, the “Institut de Biologie de Lille” (IBL), located on the “Institut
Pasteur de Lille” campus and the University of Lille 1 campus.
CHRU site
The JPARC (Jean-Pierre Aubert Research Centre, UMR 837 Inserm-University of Lille 2-CHRU, Dir
Pierre Formstecher) is localized on the CHRU site. The three research teams working on cancer
(120 people in total) use molecular and cellular approaches, with a growing use of preclinical
models. Teams are highly multi-disciplinar, putting together molecular biologists, cell biologists,
clinicians, pathologists and pharmacologists. Research is focused on the identification of new
molecular and cellular markers and targets for diagnostic and therapeutic approaches.
Elucidation of mechanisms of resistance to therapy or of escape to immune survey is a common
theme. The team “Factors of persistence of leukemic cells” (Bruno Quesnel) which focuses on
the discovery of factors that contribute to the long-term persistence of leukemic cells such as
minimal residual disease, relapse, and progression will lead the second scientific program of
ONCO Lille. The team “Molecular and cellular targeting for cancer treatment” (Pierre
Formstecher) which focuses on the characterization of cancer stem or initiating cells in skin
tumours and on the determination of the factors controlling their activation is also involved in
WP2. The team “Mucins, differentiation and epithelial carcinogenesis” (Isabelle Van Seuningen)
which focuses on the role of the membrane-bound mucins in epithelial carcinogenesis,
particularly in oesophageal, pancreatic and colon cancers is involved in WP1.
INSERM U703 unit (Serge Mordon), located on the CHRU site, is working on "Interventional
therapies image and simulation-assisted" and is oriented towards minimally invasive therapies
including laser therapy, surgery, radiotherapy, guided by multimodality imaging in preoperative
simulation, per-operative planning (interventional imaging) or post-operative situations (followup, therapeutic evaluation). The scientific project is currently based on two axes: 1) new
treatments of pelvic cancers and pelvic mobility and 2) support to vascular treatments.
The PHARMACOLOGY UNIT of the COL (Amélie Lansiaux) develops both fundamental and
clinical research projects. Studies are carried out on the adaptation of chemotherapy in patients
with oral and oesophageal cancers in the aim to reduce toxicity and to bring maximal
therapeutic effect. The laboratory of human molecular oncology (LOMH) (Jean-Philippe Peyrat)
of the COL is devoted to the research of modifications of the BRCA genes in family with
hereditary risk in breast and ovarian cancers.
Calmette site (Institut Pasteur de Lille and IBL)
UMR CNRS 8161 (Yvan de Launoit) focuses his interest on the identification of molecular
mechanisms (from membrane receptors to transcription factors) by which a normal cell
becomes tumoral, and finally metastatic. Research is performed by six independent and
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interactive teams. A special attention is given to reinforce the interdisciplinary programs. This is
for example the case of the strong collaboration between the biologists studying the HGF/SF
receptor, MET, and the chemists specialized in sugar potential inhibitor (deregulated MET
signalling is involved in tumour progression) (Oleg Melnyk). More particularly, they study the initial
events regulating the MET receptor; i.e. the proteolytic processing during development and
tumorigenesis (David Tulasne). The first steps of tumorigenesis are decorticated through the
molecular mechanisms by which a normal cell becomes pre-tumoral by escaping senescence
and/or programmed cell death (Corinne Abbadie) or by which a tumour suppressor gene can
be by-passed (Dominique Leprince). The tumour microenvironment crucial for the metastatic
process is analyzed mainly via the role of the VE-statin in tumour neo-angiogenesis (Fabrice
Soncin). Finally, interactions with the clinics are reinforced, particularly through programs on the
immune response in HCV-related hepatocarcinoma, as well as TMPRSS2-Ets induced prostate
cancer metastasis.
The University of Lille 1 campus
INSERM U908 “Growth factors signalling in breast cancer” (Xuefen LeBourhis) research activity is
focused on the role of the neurotrophin family of growth factors in breast cancer, and their
potential value for diagnosis and therapeutic intervention in this pathology. A particular
attention is dedicated to signalling networks initiated by neurotrophin receptors and leading to
cancer cell survival, proliferation, migration and metastasis.
MALDI IMAGING TEAM (Isabelle Fournier) research is focused on the development of novel mass
spectrometric methodologies and techniques for the investigation of the spatial localization of
compounds in tissue leading to the reconstruction of two-dimensional molecular maps.
INSERM U1003 “Ion channels in cancer” (Natacha Prevarskaya) is interested in the alterations of
ion channel electrophysiological properties and molecular biology during prostate
tumorigenesis. Indeed, ion channels determining the calcium signature would appear to be the
best potential candidates as tumour markers and pharmacological targets so they are
concentrating their research on the mechanisms of the regulation/modulation of several most
promising channels.
UMR CNRS 8576 “Structural and Functional Glycobiology” –UGSF (Jean-Claude Michalski) is one
of the worldwide leader institute in the field of glycobiology. They developed numerous research
activities in the field of cancer that bring important stones for the understanding of the
involvement of glycosylation in the physio-pathology of cancers, and mostly of epithelial
cancers (Philippe Delannoy and Tony Lefebvre).
EA479, “Régulation des Signaux de Division” (Jean-François Bodard), is focused on the
determination of the recruitment mechanisms and dynamics of molecular effectors activated
either by the oncoprotein Mos or by Tyrosine Kinase Receptors.
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II.2.1.2. RESEARCH IN HUMAN AND SOCIAL SCIENCES AND PUBLIC HEALTH
Research in human and social sciences applied to cancer is labelled at the national and
international level and based both on existing teams having a long experience in health project
and also on emerging resources with high potential for research against cancer. Research
activities on cancer are already strongly structured on the MESHS, a federative “service and
research unit” (USR 3185) under the tutelage of the CNRS and the Lille 3 University. It aims to
structure and promote the research in social and human sciences in the region, acting as a go
between laboratories but also between social sciences and exact sciences. They develop a
program on Health with a part on practices, representations and norms, a part on Health politics
and a part on relations between actors with the impact on medical care practice. Within the
ONCO Lille, we intend to strongly increase interactions between cognitive and informational
sciences with public health, economics and quantitative methods like econometrics and
applied statistics. Indeed, several projects focused on quantitative tools to assess from individual
data the underlying process relating cancer morbidity and mortality to decisions linked to health
behaviour and socio-economic conditions.
Lille 3 University
The URECA (Research Unit on Cognitive and Affective Sciences, EA 1059, ONCO Lille contact. Pr
Véronique Christophe). The scientific program of URECA concerns the modelling of the cognitive
and the emotional processes that determine normal and pathological interactive behaviours for
natural and artificial systems. A specific interest is devoted to the better understanding of the
conditions and the dynamics of the emergence of human behaviour in the field of health
psychology related to behavior, emotion, cognitive and familial aspects. More particularly,
URECA is very active in translational programs and since 2005 they have interacted with CHRU
and COL to develop pluridisciplinary projects in the field of the cancer supported by national
and regional grants (INCa, National League of Cancer, Nord-Pas de Calais region etc).
The EQUIPPE unit is specialized in econometrics, public policies, integration and quantitative
economy (ONCO Lille contact. Pr Jérôme Foncel). More particularly, they study times series,
spatial statistics, forecasting, micro-econometrics which are topics that can be fruitfully applied
to the definition and the evaluation of primary to tertiary preventive actions.
The GERiiCO laboratory works on information and communication sciences (ONCO Lille contact:
Dr A. Lamy). They are interested in production, transmission, diffusion and appropriation of
information, knowledge, text, and representations in contemporary and modern society. They
have methodological and analytic skills in information and communication sciences, social
sciences that are instrumental to analyse how people understand health information. They are
implicated in 23 ministerial programs and 3 regional programs of which one in health domain.
The integration of research in the field of oncology is planned for the purpose of knowledge
dissemination.
Lille 2 University
The CRDP « centre de Recherche en Droit et Perspectives du Droit, EA 4487 » (ONCO Lille contact
Pr P Frimat & Dr S Fantoni). Multidisciplinary projects are elaborated in between law and
medicine /pharmacy research teams. The study and research centre in « Health-employmentenvironment » develop within the EA 2694 a theme on public health with a section on
epidemiology of chronic diseases and a section on modelling with biostatistics and information
sciences.
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II.2.2. CLINICAL RESEARCH
II.2.2.1. CHRU LILLE
The CHRU de Lille is the 4th university hospital in France in terms of scientific publications, the 3rd
in clinical research:
Each year, the CHRU de Lille sponsors nearly 70 new studies and is investigator centre in nearly
900 studies (academic or industrial). In 2010, more than 4000 patients have been included in
clinical trials among:
500 trials promoted by institutional and academic structures representing 2 262 inclusions
383 industrial trials representing 2 000 inclusions
Particularly in the field of oncology, the CHRU de Lille promoted 24 studies in 2010, representing
428 inclusions, and was investigator centre for 298 studies in 2010 representing 685 inclusions:
159 institutional and academic trials representing 293 inclusions
139 industrial trials representing 392 inclusions
Thus, oncology field represent in the overall clinical research activity of the CHRU de Lille:
13% of overall number of studies promoted by the CHRU, representing 21% in terms of
inclusions.
34 % of overall number of studies for which the CHRU is the investigator centre, representing
16% in terms of inclusion.
Clinical research activity grows continuously since 2006, as presented below:
Tableau 1 : Number of cancer studies by sponsor
Year
CHRU
Academic
Industrial
Total
2006
15
112
84
211
2007
13
111
68
192
2008
16
139
100
255
2009
20
169
126
315
2010
24
159
139
322
Tableau 2 : Number of cancer patients by sponsor
Year
52
CHRU
Academic
Industrial
Total
2006
116
202
142
460
2007
91
282
146
519
2008
287
325
154
766
2009
317
201
279
797
2010
428
293
392
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Organization of clinical research
The CHRU de Lille has for over fifteen years initiated a dynamic support to clinical and basic
research, through the creation of the "Delegation for Research and Innovation" (DRCI) covering
both aspects.
The CHRU de Lille was the first University Hospital in France to co-sign the four-year contract
between the University and French Ministry of Higher Education and Research, and an
agreement with the University of Lille 2 and INSERM.
A tight link exists between CHRU, University, Inserm and CNRS with the constitution of mixed and
multi competent teams. These collaborations allow the creation of a university biomedical
research structure, the “Institut de Médecine Prédictive et de Recherche Thérapeutique » (IMPRT)
and the organization of the « Clinical Research Federation ». Furthermore, the CHRU and the
PRES “Lille Nord de France”, in close connection with Eurasanté and Inserm, have shared their
activities of economic valorisation in creating BIOVALO, a structure for the valorisation of the
biology-Health section.
Under the responsibility of the Delegation for Research and Innovation, the Clinical Research
Federation (FRC) is responsible for:
the instruction and the assistance in drafting clinical research projects which CHRU de Lille is
going to promote
the operational implementation of institutional and industrial clinical research projects.
The Clinical Research Federation‟s primary role is to assist the development and set up of clinical
research projects, from their submission to their operational implementation, using staff, skills,
resources and labelled structure inside the CHRU like the « Centre d‟Investigation Clinique », the
« Centre de Resources Biologiques », and others investigation support platforms.
The Clinical Research Federation (FRC) has 3 main objectives:
group together in a single structure the teams involved in professionalization of clinical
research on campus: the promotion unit, the « Centre d‟Investigations Cliniques » (CIC), the
« Centre de Resources Biologiques » (CRB), the « Centre d‟Innovations Technologiques » (CIT),
the biostatistics unit…
pooling of human and logistical resources assigned to clinical research, particularly medical
and non medical who received special training in clinical research, in order to harmonize
practices, recognize and develop employment of research professional‟s policy,
offer investigators and biomedical sector professionals a single window providing: (i) the
definition of clinical trials (methodology, logistics, medical and regulatory aspects and
financial), (ii) the implementation, monitoring and quality assurance of clinical trial.
In practice, through the FRC, the Delegation for Research and Innovation of the CHRU de Lille :
assist investigators in the establishment of their protocols (methodology, law, logistics,
financials aspects…) through consulting and support units.
coordinates and monitors the progress of projects in promotion, by its pool of Clinical
Research referents, monitoring and controlling the quality of the protocols, which is inherent
to the responsibilities of the insitutionnal promoters ;
provides investigators, when needed, the staff (ARC / TRC and other staff) required for the
day to day investigation activity linked with clinical studies.
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Clinical trials of the CHRU are conducted in:
The blood diseases unit, based at Hôpital Huriez at the CHRU in association with the 7 units of
haematology of the Fédération d‟Hématologie Régionale (CH Lens, Valenciennes, Arras,
Dunkerque, Roubaix, Boulogne et l‟Hôpital St Vincent de Paul du GHICL), takes in charge the
regional clinical research activity of adult leukaemia and lymphoma. The centre has a sterile
sector where bone marrow allograft are realized for adult patients of the whole region of
Nord-Pas-de Calais, and it has access to all technical platforms of the campus.
The paediatric haematology unit of Hôpital Jeanne de Flandre CHRU-Lille, which also work in
association with a regional network,
The multi-thematic CIC (Clinical Investigation Centre-Inserm, recently evaluated A+), with a
personnel dedicated to clinical research (physicians, engineers, clinical research associates
and technicians, administrator, data managers, …). It has specific premises (7 adult beds
including one with laminar flow, 4 paediatric beds), surveillance materials, data recording
facilities, a laboratory for preparation and pre-analytic treatment of biological resources
(PSM, …) under control atmosphere type L2, adaptable L3. Volunteers are taken in charge in
the centre in different ways: external consultations, day hospitalization, short term
hospitalization, and regular hospitalization.
Partnerships are particularly rich with imaging and nuclear medicine platforms, biology and
pathology centre where is located the tumour bank, the biological resources centre and the
central pharmacy and its clinical research sector (cytostatics reconstitution unit). Pathologies
taken in charge in these units cover the whole adult and paediatric haematology and
hematopoietic cellular grafts principally in onco-haematology
The recognition of the Lille‟s site at the national and international levels is expressed by almost
permanent external solicitations for participation in therapeutic trials, as well as the implication in
36 international groups and European infrastructural projects (ECRIN, BBMRI). Pharmacovigilance
is involved in a European FP7 project "PSIP" (Patient Safety-through Intelligent Procedures in
medication) and obtained funding from the EU up to 7.27 million euro. A specific analysis of
patients enrolled in early phase will be down also by this tool. Moreover, particular attention will
be paid to early phase trials in children to meet the needs expressed in the Paediatric
Investigation Plan and the European regulation on medicines for children recently adopted by
the European Commission.
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II.2.2.2. CENTRE OSCAR LAMBRET –THE CLINICAL RESEARCH UNIT
The Integrated Clinical Research Unit (UIRC) of the Oscar Lambret Cancer Centre assures the
development of clinical research of this establishment in accordance with the orientations and
the objectives recommended by the external scientific council and in conformity with regulatory
dispositions and Good Clinical Practice Guidelines.
This unit is composed of administrative offices, 8 rooms with beds and medical chairs for patients
within the same physical area specifically attributed to clinical research. The unit was conceived
as an interdisciplinary platform dedicated to clinical and translational research and has allowed
the inclusion of 706 patients in 158 interventional studies, which represents 12.8% of the active file
of the establishment.
Its 3 missions are the following:
The UIRC of the Oscar Lambret Cancer Centre is a pluridisciplinary investigation site open to all
players in the Region
Created in the middle of the 90‟s, the Clinical Research Unit, which became the Integrated
Clinical Research Unit in 2006, coordinates and centralises all the clinical research activity of the
Centre Oscar Lambret Cancer Centre. As of June 2010, the staff of the UIRC investigation unit
included 4 full-time ARC (including one ARC CENGePS) and 7 equivalent full-time TRC (Clinical
Research Technicians). Each ARC and each TRC is in charge of one or two cancer sites. One
ARC is responsible for applying quality control procedures.
Since 2007, the UIRC disposes of a care unit specifically dedicated to taking care of adult
cancer patients included in early phase clinical trials (phase 0, 1 or 2). This care unit is under the
medical responsibility of Pr Antoine ADENIS and is in possession of an authorisation for research
which was renewed in 2010, in conformity with the new regulations: “Biological research for
scientific purposes and notably clinical trials of first administration in Man (drugs destined for
human usage, medical apparatus), trials in radiotherapy and translational research”. The
investigators intervening within the UIRC all received training in Good Clinical Practice.
The implantation of UIRC facilitates the taking care of patients, since it benefits from a privileged
geographical position in the establishment. It is situated within immediate proximity to the outpatient hospital, as well as the Internal Pharmacy Usage (PUI) and the external consultations.
With its 8 beds and medical chairs, the UIRC is perfectly adapted to the ambulatory
administration of galeneic formulations actually developed in oncology (oral route, infusions of
short duration).
The head nurse who is responsible for the supervision of health care personnel affected to the
unit, has an ARC qualification. Besides the planning and the coordination of patient care, he
elaborates, for the patients of each new study, the procedures for specific care, taking into
account the requirements and constraints of each trial. At the present time, the nurse team is
composed of 2 IDE (Infirmier Diplômé d‟Etat), whose jobs are occupied by experienced clinical
research nurses of the Centre. In order to follow the constraints of the protocols, the patients
included in the trials benefit from reserved time slots for imaging tests as well as functional
imaging.
The Early Study Projects are managed and conducted by a single organisation allowing a rapid
implementation of the study (mean delay of 2 weeks after receipt of the CPP (Comités de
Protection des Personnes) and AFSSAPS (Agence Française de Sécurité Sanitaire des Produits de
Santé) authorisations, once the internal authorisations of the CEC (Commission des Etudes
Cliniques) of the Centre have been obtained. This commission meets monthly and insures the
scientific importance of each study in accordance with the strategic and political orientations of
the Centre and its external scientific council. If necessary, extraordinary meetings of the CEC can
be organised for rapid decisions depending on the importance of the proposed study.
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The UIRC of the Oscar Lambret Cancer Centre as a study sponsor is dynamic and efficient
Since 2004, the UIRC reinforced its activity as a sponsor of clinical trials (essentially phase II trials).
It provides methodological support, regulatory and logistic documentation for the development
of projects planned by investigators of the Centre. As such, it centralises and also sponsors
projects susceptible to enter into the scope of grant proposals from INCa (Institut National du
Cancer), notably the PHRC. The sponsor unit comprises 1 ARC project leader and 1 ARC monitor,
an assistant administrative manager of trials and a data entry operator.
The development of these projects is carried out with the support of the Methodology and
Biostatistics Unit of the Oscar Lambret Cancer Centre, under the direction of Andrew Kramar
since april 1st 2010. Since 2007, all the data from studies analysed by the Biostatistics Unit were
managed by the North-Ouest Cancéropole Data Treatment Centre (CTD-NO), according to the
standards in use. Moreover, a partnership exists with EA2694 (Santé Publique, Epidémiologie et
modélisation des maladies chroniques/ Pr A. DUHAMEL) which is attached to the Biology and
Health Doctoral School and which has a recognised expertise in the fields of data-mining,
medico-economic analyses, and bio-informatics. Finally, the pharmacovigilance of the studies
sponsored by the COL is assured by UIRC (Dr Stéphanie CLISANT) who passed the Eudravigilance
assessment.
The sponsorship activity is sustained with 507 and 432 patients included in France in trials
sponsored by the Centre Oscar Lambret Cancer Centre in 2009 and 2010 respectively. This
activity allowed the UIRC to receive financial assistance for 19 PHRC since 2003, 9 of which were
obtained within the last 3 years (3 in 2008 ; 2 in 2009 ; 4 in 2010).
The partners implicated in the translational part of these clinical studies: The Cancer
Pharmacology Laboratory (Dr A. LANSIAUX, MCU-PH), and the Human Molecular Cancer
Laboratory (Pr JP. PEYRAT) of the Oscar Lambret Cancer Centre.
The UIRC of the Oscar Lambret Cancer Centre is also a training and research site for Behavioural
Sciences
The UIRC is a training ground for medical internship (DES Medical Oncology and DESC of
Oncology) as well as pharmacy and students from ILIS (Institut Lillois d‟Ingénierie de la Santé)
who are in training for jobs as TRCs and ARCs.
More recently, interdisciplinary research activities were developed in partnership with the Lille
Nord de France University (Dr V. CHRISTOPHE) on the subject of the patient‟s perception and
comprehension of informed consent, the study of the psychological and emotional impact of
patient participation in a cancer clinical trial, or how doctors live with the announcement of bad
news. Four transversal projects are in progress and are entirely supported by INCa, the Ligue
Nationale contre le Cancer, the Fondation de France and pharmaceutical industries
The Cooperative Sanitary Group “Centre de Référence Régionale en Cancérologie (C2RC)”
created by the COL and the CHRU of Lille favourites cooperations in the domain of clinical
research in oncology between the two establishments.
The C2RC has as an objective the development of a common medical and scientific project
between the CHRU of Lille and the Oscar Lambret Cancer Centre. Under the auspices of the CIC
of the CHRU of Lille, the two establishments signed a contract in 2008 which enabled clinicians of
the CHRU of Lille to openly cooperate with the UIRC of the COL.
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II.2.3. TRANSLATIONAL RESEARCH
The CHRU blood diseases unit participates in fundamental research in the domain of the
mechanisms of tumour dormancy in collaboration with the laboratory of the faculty of
pharmacy and pre-clinical models are in development (Pr Quesnel, Inserm 837).
The emergent translational clinical research activity is now structured and permits participation in
a dozen of trials since 5 years. In 2009, 168 therapeutic trials were initiated in the blood diseases
unit:
87 trials with a public organism or cooperating group as sponsor (119 inclusions, 433 active
patients)
78 trials with an industrial sponsor (150 inclusions, 255 active patients)
Activity in early phases (phases 0, preferentially called “exploratory”, phases I, and phases II) is
regular since 2000, with the participation in 135 trials (1 phase 0, 14 phase I, 20 phase I/II, 100
phase II) from a dozen projects per year to reach 21 new protocols in 2009. 64 were still active
phase studies with a queue of 185 active patients until the 31th of December 2009. This has
contributed to the obtainment of the AMM of ZEVALIN®, GLIVEC®, REVLIMID®.
In 2009, 19 trials concerned phases I or I/II with a first administration to man, 62 phases II. Many of
these trials are pivot ones for registry of new molecules in oncology.
Beside investigators and medical teams, clinical research team, directed by Dr. Marie-Odile
Pétillon is composed of:
1 senior clinical research technician, in charge of the coordination, training and managing of
the clinical research technician team and working for 4/5 of time.
10 clinical research technicians 7.5 full time.
1 clinical study nurse in charge of patient‟s hospitalization.
2 secretaries for document‟s management and office work.
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II.3. Presentation of the SIRIC shared resources and facilities
II.3.1. 4 INTEGRATED PLATFORMS
To be more efficient, we have developed the concept of Integrated platforms defined as
“shared resources including facilities, infrastructures and human competences dedicated to the
scientific programs for research and training”.
The CHRU of Lille and its partners have at their disposal a pool of integrated platforms and
biological resources that provide them the necessary equipment to develop innovating research
projects in the field of cancer. Equipped with state-of-the-art apparatus and staffed by highly
specialized personnel, the Integrated Platforms will provide support services with highly
competitive technologies and will actively participate in research projects, platform networks,
technology development projects and agreements.
They are characterized by their strategic value, which makes them core assets for the
implementation of public and private research.
They represent another originallity of the program with the capacity to mobilize all facilities in a
combined way, in order to make possible the programs with the best possible efficacy.
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II.3.2. INTEGRATED PLATFORM 1: BIOLOGY
To tackle the biological questions raised in the two scientific programs, the present project will
benefit from all the top-quality expertises available in Lille and more particularly within the CHRUCOL, Lille 1 and Pasteur Institute campuses. In fact, they have at their disposal a pool of
biological technology platforms and resources that provide them the necessary equipment to
develop innovating research projects in the field of cancer, for example to decipher the
molecular pathways directly involved in tumour resistance and tumour dormancy.
Over the last years, the functional genomic platform permitted to identify new crucial genes
involved in acute myeloid leukaemia. Now, it will be applied to tumour dormancy and
immunoevasion projects for this disease, as well as for the solid tumours studied in the second
scientific program. In fact, this facility will identify and analyze genetic alterations (DNA and RNA)
such as mutations and/or overexpression of receptor tyrosine kinase (RTK) and mucin genes (first
scientific program) or specific factors associated with tumour dormancy in AML, melanoma and
prostate cancer (second scientific program). A top-quality tumour library platform common to
the CHRU and the COL will play a key role for the success of this project, more particularly the
identification of the tumour samples necessary for the goals here above mentioned. Proteomic
studies (in coordination with the Glycobiology platform) will also be performed in both scientific
programs, and more specifically new cell determinants and signalling pathways involved in
resistance (signalling of RTK). This project will also reinforce the collaboration with the Peptide
Chemistry platform to characterize new RTK inhibitors.
The key results obtained in these programs will be translated into pre-clinical mouse models
(spontaneous/induced or humanized models...) for example to determine physio-pathological
processes linked to primary or secondary tumour resistance (oesophageal cancer) or tumour
dormancy and immunoevasion. The more promising data obtained on mouse tumour models
will be developed in dog and cat by Oncovet pharma which has a large access to animals with
spontaneous tumours. The use of these spontaneous tumour models arising in dogs and cats with
similar natural history and response to treatment will be a great value (originality) in the
ONCO Lille program.
Equipped with state-of-the-art apparatus and staffed by highly specialized personnel, the
Biology Platforms of the site provide support services with highly competitive technologies. These
platforms not only offer services but they also actively participate in research projects, platform
networks, technology development projects and agreements. These platforms are characterized
by their strategic value, which makes them critical for the public and private research and
development sectors. The main activities developed by the Integrated Platforms are devoted to
research support, technology development (establishment of new methodologies) and research
projects and they can be co-managed by several institutes demonstrating the aptitude to work
in synergy for technical, medical and research staff. Indeed, these resources are accessible to
the whole of the Lille scientific community with a specific organization and often with a scientific
committee which evaluate the appropriateness of the project with the proposed technical
resources. Some of them are federated at the regional level and detain the national label
“IBiSA” (“Infrastructures Biology Santé Agronomie”) allocated by the AERES (“Agence
d‟Evaluation de la Recherche et de l‟Enseignement Supérieur, i.e National evaluation agency
for research and Higher education). This label is a guarantee of excellence and opening of the
platforms. The platforms are also highly active in terms of education to the use of new tools and
in technology watch. The regional scientific community uses every effort to open the integrated
platforms to the researchers and to favour interactions between clinicians and fundamental
researchers. For example, the organization of “clinicians-researchers day” within the context of
the PHARE-project “cancer” of the CPER (Contrat Plan Etat Région) had a strong impact on the
development of translational research in the region.
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Functional Genomic Platform
Management and contact
 Dr Martin Figeac – manager of the Genomic platform, IRCL
 +33 3 20 16 92 20
 [email protected]
Location

CHRU, Place de Verdun 59045 Lille cedex
Key figures / Key features
The objective of the genomic facility is to empower the biomedical teams working in the field of cancer in
particular, to develop large scale genomic project and assist them in exploitation of the generated data.
 Belonging to the multisite platform LIGAN (labelled IBiSA), this equipment was certified by IBiSA (BiologyHealth-Agronomy Infrastructures) in 2009. The network LIGAN provides access to the latest high throughput
genotyping tools (454/ HiSeq-2000 / SOLiD, iSCAN, Bead Array and Bead Express).
 90% of its activity is dedicated to cancer.
 Localization of the platform inside the CHRU site, giving an easy access for SIRIC projects
 A high-qualified permanent team : 11 people, 6 working on molecular biology aspects and 5 on bioinformatics,
biostatistics and IT.
The functional and structural genomics platform conducts about 30 projects a year involving about 1000 samples
analyzed. The platform is deeply committed to cancer research projects and has been involved in many high level
publications in the field.
Team involved in ONCO Lille
- Lille 2 University – IFR-114 – IRCL – UMR 8161, UMR Inserm U837 E3 and E4, Laboratory of haematology CHRU
Description (skills & resources)
Since May 2009, 4 distinct and complementary technical units :
 AGILENT and AFFYMETRIX, which involve the most widely used microarray technologies
 SOLiD 4 system, devoted to high throughput sequencing (enables the resequencing of entire genomes or
more pragmatically targeted DNA genome regions, and also to quantify transcripts mRNA and small RNA, to
reconstruct different isoforms and their mutations, as well as to quantify epigenetic processes.
 The Bioinformatics Unit, manages computerised and statistical studies of results obtained with DNA chips and
by sequencing.
The platform is part of the LIGAN-MP (personalized medicine LIGAN EQUIPEX) and will develop in the next ten
th
ut
nd
rd
years high roughp sequencing (2 and 3 generation) for patient care.
Main assets for ONCO Lille
Genomic platform will supply technical support to the realization of SIRIC projects in the identification and
analysis of genetic alterations, in basic research and in translational research. For example :
 Identification of mutations and/or overexpression of RTK (MET, EGFR …) genes and MUC genes (program 1)
 Characterization of specific factors associated with tumour dormancy in experimental melanoma (program 2)
 Translational research for the program 1 (predicting relapse - acute myeloid leukaemia)
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Tumour Bank
Management and contact
 Marie-Christine Copin, Coordinator of the C2RC tumour
bank and of the regional network
 +33 (0)3 20 44 49 85
 [email protected]
Location
 Centre de Biologie et pathologie – CHRU – 59000 Lille
Key figures / Key features
The function of the tumour bank is the cryopreservation of cell and tissue samples suitable for molecular studies
relating to DNA, RNA and proteins. Its mission is to organise and manage collections of frozen tumour cell and
tissue samples and as frequently as possible healthy tissue samples from CHRU and COL, together with biological
and clinical annotations. The samples come from the CHRU and COL, but also from other private or public
establishments in the region, via the regional tumour bank network (approved and funded by INCa, 60 healthcare
establishments or anatomical pathology laboratories).
In this way, the tumour library contributes to the development of oncology research aimed at improving
diagnostic and therapeutic care of patients (1,079 samples were used for research in 2009), as well as the
development of diagnostic, prognostic and therapeutic innovations in oncology, excluding cell therapy.
Team involved in ONCO Lille
 CHRU: Pathology department and haematology laboratory
 COL: Pathology department
 UMR 8161, U1003
Description (skills & resources)
Staff: Surgeons, pathologists and oncologists are implicated in the management of the resources.
Equipment:
 In 2009, the HCCRB software application was installed (Technidata) for the management of the samples in the
Lille CRRC tumour bank and all the tumour banks within the Cancéropôle Nord-Ouest cancer hub.
 Appropriate data are available for each type of cancer in the HHCRB software application.
Recent developments:
 Grant of €250,000 obtained from INCa for the organisation of the molecular pathology centres.
 Application for “IBISA” accreditation: budget of € 45,000 obtained to support the tumour library’s quality
assurance system (employment of a part-time quality technician).
A high level of scientific production: in 2009, 11 publications for cell library, and 7 publications for tissue library.
Main assets for ONCO Lille
The tumour library plays a fundamental role in the development of preclinical and applied research in oncology,
offering researchers the means to access comprehensive sets of biological samples linked to broad clinical and
biological data. For ONCO Lille, tumour library will support the scientific programs :
 the first one, particularly in the study of the role of the membrane partners of RTKs in resistance to locoregional treatments (mucins and oral and oeso-gastric cancers)
 the second one : in basic research (intracellular calcium and membrane ion channels in prostate cancer, bone
metastasis in prostate cancer) and in translational research for predicting relapse in acute myeloid leukaemia
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Tumour genetic
Management and contact
Pr. Nicole Porchet – Medical manager of the platform, CHRU
 +33 (0)3 20 44 61 54
 [email protected]
Location
 CHRU Lille, Centre de Biologie et Pathologie, 59 000 LILLE
Key figures / Key features
The CRRC Tumour Molecular Biology Platform was set up to carry out newly-developed molecular tests as part of
the care of cancer patients in the region. The tests relate to predictive markers which will determine patients’
access to particular targeted treatments, markers of diagnosis or prognosis or for follow-up of residual disease.
The molecular tests complement the anatomical pathology diagnosis for all cancers, or the biological diagnosis for
leukaemia. The CRRC’s biologists belong to national networks for the purpose of standardising tools and quality
control and the CRRC pathologists belong to diagnostic expertise networks in fields for which molecular analysis is
essential (sarcomas, lymphomas, brain tumours).
2010 workload: over 6000 tumours analysed (half in haematological oncology, half solid tumours); approximately
20,000 tests carried out.
Team involved in ONCO Lille
 CHRU Haematopoietic tumours : Cellular haematology department (Prof. C PREUDHOMME), Haematological
oncology cytogenetics training unit (UF), Medical Genetics department (Dr JL LAÏ)
 CHRU Non-haematopoietic tumours (solid tumours and sarcomas) : Anatomical pathology and cytopathology
Institute (Prof. Marie-Christine COPIN), “Endocrinology, metabolism, nutrition and oncology” biochemistry and
molecular biology department (Prof. Nicole PORCHET), Joint Molecular biology, genetics and cytogenetics
platform of the Biology Pathology Genetics Centre of the CHRU Lille (Prof. Nicole PORCHET)
 COL Non-haematopoietic tumours: breast cancer : Human Molecular Oncology Laboratory (Prof. JeanPhilippe PEYRAT); Anatomical Pathology and Cytopathology Laboratory (Dr Yves-Marie ROBIN)
Description (skills & resources)
Multiple facilities including :
 Tools for Molecular biology: 5 capillary sequencers, 1 pyrosequencer, 2 real time PCR systems, automated preand post-PCR systems pending delivery; 1 next generation genome sequencer (GS Junior Roche) in the process
of being purchased; 1 Agilent array CGH platform, 2 automated DNA extraction systems.
 Culture platform with an L2 laboratory for the study of human cells, yeasts and bacteria for molecular biology
cloning.
The workload is continuously growing: work on solid tumours (number of analysis) has increased by nearly 60%
between 2009 and 2010 and in terms of haematological oncology work (regional and national), 15927 analyses
were performed in 2010, according to a 61 biomarkers list.
Main assets for ONCO Lille
 The platform is currently involved in different activities in basic research, translational research and diagnosis
fields and is in close interaction with researchers and clinicians of the site.
 Expertise in related activities and quality of service
 Location of the platform inside the CBP ; giving an easy access for the SIRIC’s teams
 Particularly, the platform will provide useful tools for identification of the role of the membrane partners of
RTKs in chemoresistance.
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Proteomic and glycobiology platform
Management and contact
Pr Christian Rolando – Director, Laboratoire de Biophysique,
Faculté des sciences pharmaceutique et biologiques
+33 3 20 43 49 97
[email protected]
Location
 University of Lille 1, Cité scientifique, 59655 Villeneuve d’Ascq
Key figures / Key features
Localized in the University of Lille1, the proteomic and glycobiology facility is a multi equipment tray from
proteomic to glycotechnologies. The proteomic platform is labelled IBIsa.
Team involved in ONCO Lille
UMR 8161, INSERM U908, UMR CNRS 8576, U837 E3 and E4
Description (skills & resources)
Common centre of mass spectrometry - Scientific coordinator: Christian ROLANDO :
 Material: MALDI-TOF, ESI-ion trap et logiciels dédiés, Nano-LC couplée au piège ionique
 Users: All units if the IFR, external academics (IMPRT, Institut Pasteur, IBL) for 30 %, and industrials for 10 %
Tray of proteomic Hi_Prot Scientific coordinator: Caroline TOKARSKI
 Material: Mass spectrometers, systems for Sample preparation, Robots, Bidimensional electrophoresis,
Software of imaging analysis, Quantitative Proteomics, Data treatment
 Users: IFR : 50 %, external academics 20 % (CHR G. Pompidou, Musées de France, O. Lambret Centre),
Industrials : 30 % (Etablissement Français du Sang Nord-de-France, Biosynthec)
Tray of glycotechnologies Scientific coordinator: Jean-Claude Michalski
 Material: Chromatograf, phase gaz, HPLC, MALDI TOF/TOF et ESI Q-TOF (common with proteomics),
Enzymatic analysis and lectinic, Chemistry Fragmentation, Spectromètre RMN Avance 400 MHz (9,4 Teslas)
(Centre Commun de Mesures RMN de Lille 1)
 Users: IFR : external academics (IMPRT, Pasteur Institute of Paris and Lille, IBL, French and foreign universities,
CNRS, INSERM), Industrials (Sanofi, ASSAPS, Fabre).
Plasmonic Surface resonance Scientific coordinator: Dominique Legrand
 Material: Biaccore 3000
 Users: IFR: 70%, UMR 8576, FRE, UMR, external academics: 10 %, Industrials: 20%
RMN and tray of structural glycobiology Scientific coordinator: Guy Lippens
 Material: Spectrometers RMN Bruker
 Users: IFR: ERI 8, FRE, UMR 8576, external academics (IBL, IPL, INRA, CNRS/Montpellier), industrials (Aventis)
Main assets for ONCO Lille
 High qualified engineers in charge of each component of the platform, with a specific and dedicated
management team to control the access, work on equipment financing, conduct users
 A strong activity in cross-disciplinary research, and a strong link with cancer biology
The platform will provide a useful tool to the integrated programs of ONCO Lille, for example to identify cell
determinants and signalling pathways involved in resistance or to characterize specific factors associated with
tumour dormancy in experimental melanoma.
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Peptide chemistry systems
Chemistr
y
O
Management and contact
H
N
HN
N
H
O
O
H2 N
NH
S
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System
s
Biolog
y
 Dr Oleg Melnick – Institut de Biologie de Lille
+33 3 20 87 12 14
[email protected]
Location
 Institut de Biologie de Lille, 1 rue du Pr Calmette- 59000 Lille
Key figures / Key features
The originality of this platform is to combine 3 complementary areas of expertise:
 the peptide and ligation chemistry,
 the design and use of peptide-based systems such as microarrays
 the design of cellular/biochemical assays related to signal transduction by RTKs.
Team involved in ONCO Lille
UMR 8161 CNRS, Oleg Melnick, Jerôme Vicogne,
Description (skills & resources)
Team: 1 Research director, 1 engineer, 2 technicians.
Equipments (a precise description of the equipment and fields of expertise can be found at the following address :
http://csb.ibl.fr)
 AlphaScreen® and Biacore® 2000 detection systems for studying binding between two purified molecules in
solution or for quantifying signalling pathways on cell lysates.
 MALDI-TOF and one analytical LC-MS systems for the characterization of molecules by mass spectrometry
 Two peptide synthesizers, six preparative or analytical HPLCs, one preparative LC-MS system, one capillary
electrophoresis system, two lyophilizators, one glove box for peptide or protein total synthesis
 Three microarrayers (one non-contact piezoelectric, two contact system) and one microarray fluorescence
scanner (Tecan) for microarray production and reading
Scientific expertise: in Peptide chemistry, protein total synthesis and in surface chemistry applied to micronanosystems.
Application domains: Protein total synthesis, peptide synthesis, epitope mapping, characterization / detection of
antibodies, peptide / protein or protein / protein interactions, biochemical or phenotypic cellular assays related to
RTK signalling.
Main assets for ONCO Lille
 A strong activity in cross-disciplinary research
 A strong link with cancer biology with innovative translational approach
 Particularly, for ONCO Lille, the platform will provide innovative approach to take part in a bi-disciplinary
project on HGF/MET signalling with two sections consisting respectively of :
- a study of MET signal transduction leading to biological responses
- the design of novel cancer strategies targeting the MET tyrosine kinase receptor and heparanase.
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Biotherapy platform
Management and contact
Pr Francois Pattou
+33 3 20 44 42 73
[email protected]
Location
 University of Lille II, Faculty of Medicine 1 Place Verdun 59045 Lille
Key figures / Key features
The biotherapy platform, which belongs to the Institute of Predictive Medicine and Therapeutic Research (IMPRT
– IFR114), is strictly reserved for the preparation and production of human cells for therapeutic purposes. The
goal of this platform is to provide the best environment to develop new clinical protocols in biotherapy.
Team involved in ONCO Lille
UMR INSERM 837, E4
Description (skills & resources)
The biotherapy platform, dedicated to the production of cells for clinical trials, is currently involved in three
cellular therapy projects in the field of diabetes, cancer and cardiovascular diseases.
The biotherapy platform consists of premises divided into two atmosphere-controlled work zones:
 R & D zone for teams starting a protocol. This zone contains an ISO 7 clean rooms used for developing
procedures and protocols that will subsequently be examined by AFSSAPS. Research teams who wish to use
the biotherapy platform must submit a clinical protocol to the scientific committee, made up of clinicians and
scientists.
 clinical zone (ISO classes 6 to 8 clean rooms) which comprises
- 3 clean rooms: Each room is equipped for the production of cells for therapeutic purposes (microbiological
safety cabinets, incubators with C02 supply, centrifuges, lab bench consumables, microscope, vacuum
inlet…). The equipment provided for the teams meets the standards and controls set by AFSSAPS (only
teams who have official authorization to begin a clinical protocol are allowed access to the clinical zone).
The biotherapy platform also complies with the specifications laid down by the Environment office of Lille
Regional University Hospital (CHRU), which inspects the facility each year. The equipment provided in the
clinical zone comprises:
- wash room, consumables store room and room dedicated to cellular storage.
Specialist biotherapy technicians maintain the facility. These staff members are directly involved in the clinical
protocols, thus providing technical knowledge and assistance.
The platform is closely located to the university hospital providing the availability of human cells with all ethical
rules and to the Inserm units allowing the development of translational research programs.
Main assets for ONCO Lille
 The platform gives the opportunity to translate research programs from the laboratory to the clinic.
 Free access based on specific project
 A strong activity in translational medicine
Specific contribution for ONCO Lille: Laurent Mortier, Dermatologist at the Dermatology Department of CHRU
Lille is conducting a phase I/II clinical trial of immunotherapy in metastatic melanoma to improve the efficacy of
immunotherapy derived from dendritic cells. The autologous dendritic cells are produced at the biotherapy
Platform by Philippe Marchetti’s group (Inserm U837-E4).
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II.3.3. INTEGRATED PLATFORM 2: IMAGING
Biophotonic
In vitro Imaging
Cellular Model
Functional
Imaging
Molecular
Imaging
In vivo Imaging
Patients
Ex vivo Imaging
Biopsies
Animal
Imaging
In vivo Imaging
Model Animals
ONCO Lille Imaging platform (OIP) is based on integrative already imaging platforms and
research teams devoted to in vivo imaging combining MRI, PET/MRI, PET/CT, a biophotonic
platform labelled as an Equipex and molecular imaging using mass spectrometry imaging
technology for ex vivo molecular imaging.
This is the first time that in vivo, ex vivo, biophotonic and molecular MSI technology are
combined in a same platform and devoted to cancer pathologies.
OIP will offer a high added value in both clinical aspects of the resistance to treatment or
dormancy on cancer but also in a fundamental aspect by understanding the molecular pattern
of the biomolecules involved in course of diseases progression, resistance and dormancy. Such
imaging technologies integration will make the OIP a highly interdisciplinary structure offering
translation from technological and methodological developments to biological and clinical
applications.
By integrating Mass Spectrometry Imaging (MSI) and biophotonic OIP open the door of
fundamental research for physiopathological mechanisms understanding by tracking known
compounds or looking to the discovery of new markers. It is clear that identification of new
markers of pathology will give access to better understanding of signalling pathways and will
be useful for defining new therapeutic targets and thus find new treatments.
By combining MSI, biophotonic, in vivo imaging technologies and pathological platform OIP
will give access to a better clinical diagnosis and prognosis, a better patient following with a
clear objective at least a better care of patients and to shift to a medical personalized.
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In this context, two projects within the framework large program calls for ten years investment
launch by French government have been proposed and will integrate the OIP if accepted i.e.
EQUIPEX SPIDER MASS and Infrastructure MI2 project complementary to the EQUIPEX ImagInEx
BioMed and SMART.
SPIDER MASS is dedicated to promote the development of a new MS instrument for translation
of MSI from on tissue section ex vivo imaging to in vivo real time imaging for patients directly in
the operating room. In fact, this new instrument will be based on the use of laser fibers to
promote tissue ablation with subsequent analysis using MS. SPIDER MASS will aim in allowing for
diagnosis of a suspected tumour to be performed with minimal damage to the patient. This
would also give access to subsequent treatment by the same fibers using Photodynamic
Therapies (PDT) to destroy only the volume of tissue that corresponds to cancerous cells or
cells already changing phenotypes.
MI2 will be a national infrastructure that aims to integrate the analytical capabilities of
molecular imaging mass spectrometry (IMS), data validation by histology, bioinformatics
treatment of high-speed data that are generated to increase knowledge of physiology and
human diseases and contribute very significantly to progress in the field of health. It will gather
the four major national players in the field of ISM, each leading a highly complementary
techniques currently used (MALDI, SIMS and LA-ICP), 2 platforms and a histopathology
laboratory already heavily engaged in the collection, analysis, processing and visualization of
multimodal data.
ImagInEx BioMed project aims to establish a set of microscopic high-throughput screening and
analysis of very high resolution. This platform will allow identification of new therapeutic targets
and drug development faster, whose action on many diseases can be tested simultaneously
SMART (Multiple Acquisition in Resonance and Tomography) EQUIPEX aims to reinforce
multimodality functional imaging at Lille hospital. The acquisition of a new PET/MRI machine will
provide answers to physiological and physiopathological questions which cannot currently be
answered, thanks to the specificity of this new instrument for the simultaneous acquisition of
functional data from two modalities. This project includes industrial collaborations: Siemens for
the clinical research on a larger scale, particularly with partnerships with the Munich and
Tübingen teams, as well as for the methodological research on protocols for the simultaneous
acquisition of PET and MRI data and Aquilab for the quality controls in medical imaging. In the
field of oncology, this instrument will be use to explore different organs or pathologies such as
prostate, liver, head and neck tumours.
SIRIC Imaging platform have two main objectives :
to offer a strong support based on a large platform of multimodal imaging including various
types of instrumentations and excellent scientific background for helping in the objectives
fixed for the two research programs
to develop new methodologies and technologies in order to provide new cutting-edge
technologies for fundamental and clinical research and ultimately for patients opening
towards personalized medicine.
All the available technologies form together a highly integrative workflow with translation from
fundamental research to patient‟s bedside applied from cellular models up to patients through
small and medium size models of different cancer pathologies in order to provide highly
valuable data on morphology and anatomy at various scales ranging from nm up to mm scale
for cell organs, cells and tissues or molecular data on targeted compounds localization or
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looking for new regulated molecules and therapeutic targets as well as to understand action
mechanisms of drugs. The general idea is to provide a platform starting from evaluation of
patients using functional imaging to highlight cohorts with resistance to treatments and enter the
workflow to come back to the patient with a solution that will be personalized according patient
background (genetic, epigenetic, environmental & social factors).
This comprehensive imaging platform includes state of the art equipments in medical imaging
(see later) at the CHRU and at the COL and in radiation Oncology at the COL.
The radiation Oncology Department at the Centre Oscar Lambret is a leading Department in
France and Europe with its equipment and collaboration programs with international colleagues
and manufacturers.
The clinical and technological developments are at the forefront of the research in radiation
oncology in Europe around stereotactic and IGRT/IMRT treatments. Recent developments have
been performed in adaptive radiotherapy for head and neck and gynaecological tumours. A
national program, headed in Lille, is starting to validate the impact of modern technologies
(IGRT/IMRT) in treatment of aging women.
Collaboration is starting with colleagues from Bruxelles and Leuven for considering the
implementation of protons beams in clinical research and care (paediatrics, brain, prostate...).
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Cell Imaging and cytometry (Platform BICEL, IBiSA)
Management and contact
Dr F. Lafont,
Tel: +33 (0) 3.20.87.11.36
http://www.bicel.org/
Location
 Bioimaging Center Lille-Nord de France, IBL, 1 rue du Prof Calmette,
59021 Lille
Key figures / Key features
BICeL platform is a highly competitive platform member of the national infrastructure (GIS-IBiSA) and selected for
the National Programme of investments for the Furure (PIA-EquipEx). BICeL mainly dedicated to high resolution
analysis and dynamic molecular interactions mapping. It offers therefore a broad range of applications for clinical
studies and is perfectly well suited for studying cancer diseases. BiCel offer an original platform for screening
using microscopy of active compounds with therapeutic vocation, vaccines as well as multi parametric screening
of gene expression extinction on cellular dosage.
Team involved in ONCO Lille
 CNRS UMR 8161, Institut Pasteur de Lille, University of Lille North of France
 USR 3078 Institut de Recherche Interdisciplinaire, University Lille 1, University of Lille North of France
 Centre de Recherche JP Aubert, Institut de Recherche sur le Cancer IRC, University of Lille North of France
Description (skills & resources)
BICel gathers human resources and equipments from three sites: Lille University for Sciences and Technologies
(IFR 147), CHRU (IFR 114) and the Institut Pasteur de Lille (IFR 142). The Facility is organised with a general
manager and 5 departments including a highly qualified staff for each. Its development has been original and
based on technologies not existing elsewhere in France, e.g. AFM (atomic force microscopy) couped to superresolution biophotnic methods, specific multimodal imaging systems. BICel provides services in all fields of
microscopy: near field, electron, photonic and in flow cytometry. BICel is involved in many oncology projects
(U800, calcium imaging in oncology, Oscar Lambret Centre, U837, signalling and cancer, University of Lille 1,
oncology, CHRU). It also routinely proposes dynamic imaging strategies and interactions of the living (multiphoton, FRAP, FRET, FLIM, FCS, AFM, TIRF, PALM/STORM, STED), cell and molecular biology resources and
infrastructures in order to adapter labelling with techniques of FRET, FCS, FRAP, photo-activation, … as well as
infrastructures S2 and S3 on the Pasteur campus to conduct work requiring observations in vivo in a confined
environment. BICeL is an important partner of several local and international companies (Leica Microsystems,
Nikon, Osyris, Veeco, Zeiss, Roquette, Saint Louis Sucre, DIAGAST, NOVEON).
Main assets for ONCO Lille
BICeL Facility will be used to image with high resolution known molecules which are key players of carcinogenesis
mechanisms and follow the distribution at the subcellular level of this compounds. Various imaging can be used in
order to obtain information on molecules interaction or to study membrane properties of cells of different
phenotypes such as normal and cancerous cells or resistance cancerous cells. High-throughput screening and
high-content analysis will be performed in the context of prostate cancer.
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Molecular Imaging
Management & contact
FOURNIER Isabelle, Professor,
Tel: +33 320 434 194 ; FAX : +33 320 434 054
[email protected]
Location
 Bât SN3, University Lille 1, F-59655 Villeneuve d’Ascq Cedex
l
 http://www.maldi-imaging.com
Key figures / Key features
Molecular imaging platform is a multi and transdisciplinary platform with translational research from clinics to
fundamental research aiming in identifying new markers of carcinogenesis mechanisms, tracking known markers,
following distribution of drugs and corresponding metabolites (DMPK, ADME studies).
Team involved in ONCO Lille




Fundamental & Applied Biological Mass Spectrometry, EA 4550 (Pr. I. Fournier)
Pathology Institute, Lille Hospital, C2RC (Pr. M-C. Copin)
Gynecologic Clinic, Lille Hospital (Pr. D. Vinatier)
Gynecologic Service, Centre Oscar Lambret (Pr. E. Leblanc)
Description (skills & resources)
The MALDI Imaging Team (MIT) from FABMS laboratory is one of the world leaders in the field of a new emerging
cutting-edge technology which is MALDI Mass Spectrometry Imaging (MALDI MSI). MIT was the first in Europe to
have introduced and developed this novel technology in 2002 and was initiated in 2004 with a national Starting
grant (ACI Jeunes Chercheurs) obtained by Dr. I. Fournier. Since 2004 the team had shown is expertise in the field
of MALDI Mass Spectrometry Imaging and is now recognized as a major player in the international community.
From MIT has emerged in 2009 a start-up, IMABIOTECH SAS located at Eurasanté, Lille, dedicated to MALDI MSI
of drug. MIT is working since several years in close relation with gynecologic clinicians from Lille Hospital and
Centre Oscar Lambert for ovarian cancer where MSI has proven is interest to identify new markers of these
carcinomas giving further insights on the role of immune tolerance in the pathology.
Many resources are available for Molecular imaging this includes the scientific knowledge on various aspects that
are clinics, pathology, basic research as well as equipment resources. This include all instruments for pathology
studies (robots for histology or IHC) and large equipments for Mass Spectrometry Imaging namely 3 mass
spectrometers (MALDI-TOF/TOF Ultraflex II Bruker Daltonics, MALDI-LTQ orbitrap XL Thermo Fischer and ESI-IT
Esquire HCD Ultra Bruker Daltonics), 2 deposition devices (ImagePrep microsprayer Bruker Daltonics, CHIP 1000
microspotter Shimadzu), 1 nanoLC (Ultimate Dionex), 1 micro extraction microfluidic nanoESI system (LESA
Triverda Nanomate ADVION) plus dedicated bioinformatics tools.
Main assets for ONCO Lille
Molecular imaging is perfectly well suited for application in oncology. It will be used as an integrated tool for
studying different aspects of resistance, relapse and dormancy. Molecular imaging using cross-validation in
between histology and Mass Spectrometry Imaging (MSI) can be used to follow at the cellular level specific known
molecules suspected to have an important role in resistance, relapse and dormancy. On another side it can also
be used as a discovering tool for determining variation in molecular composition (metabolites, lipids, peptides
and proteins) and identifying key factors of mechanisms using as basic knowledge to better understand signalling
pathways underlined by the regulation of these factors. Moreover, MSI can be used to study the distribution of
new therapeutics or to study action mechanisms of specifics treatments. At longer term MSI is to be developed
for in vivo imaging as a diagnosis tool for patients.
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Medical Imaging
Management and contact
Pr Damien Huglo
 Tel : +33 3 20 44 67 93 / Fax : +33 + 20 44 47 88
 [email protected]
Location
 Nuclear Medicine, Hospital Huriez, CHRU of Lille, 59037 Lille
Key figures / Key features
Medical imaging is available on both sites of C2RC, the Lille University Hospital and the Centre Oscar Lambret. Both
sites own several instruments, of high performances and complementary.
The imaging facilities include the Nuclear Medicine Departments and the Radiology Departments. The main
objectives of these groups are to identify the best imaging markers for early diagnosis of cancer and its staging and to
identify specific tools for post-treatment follow-up.
Team involved in ONCO Lille







Nuclear Medicine Clinic, Lille University Hospital (Pr Franck Semah)
Radiology Clinic, Lille University Hospital (Pr Jean-Pierre Pruvo)
Nuclear Medicine Department, Centre Oscar Lambret (Dr Philippe Carpentier)
Radiology Department, Centre Oscar Lambret (Dr Luc Ceugnart)
Radiation Oncology, Centre Oscar Lambret (Pr Eric Lartigau)
INSERM U703 "interventional therapies Assisted by Image and Simulation" (Dr Serge Mordon)
Clinical Departments of Lille University Hospital and Centre Oscar Lambret
Description (skills & resources)
Each main building of Lille University Hospital and Centre Oscar Lambret own its radiology site. There are also 3
nuclear medicine sites located at Hospital Huriez, Hospital Salengro and Centre Oscar Lambret. The medical imaging
platform includes 7 MR units (with a 3T MR Scanner dedicated exclusively to research work), 13 CT scanners, 9
angiography rooms and 28 ultrasound machines in the Radiology Departments and 8 gamma Cameras (all SPECT
including 3 SPECT-CT) and 2 recent PET-CT systems GEMS) located in the Nuclear Medicine Departments. The
forthcoming commissioning of a cyclotron on the Lille University Hospital site will provide PET tracers for biomedical
research. All structures have a PACS and the communication between Lille University Hospital and Centre Oscar
Lambret systems is planned. A clinical PET-MRI machine is asked in the Equipex program (SMART project).
Main assets for ONCO Lille
 Complete and recent medical imaging platform with some equipments dedicated to research work
 Important and regional patient recruitment with strong expertise from imagers in specific domains
 Strong collaborations between clinical physicians, researchers on treatments based on dynamic phototherapy
(PDT) or laser thermotherapy (LITT), radiotherapy or surgery and imagers in a lot of fields of oncology (urology,
haematology…)
 Important connections between methodological (acquisition, segmentation, integration of PET and MRI
anatomical and functional information …) and clinical projects.
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Animal Imaging (IMPRT)
Management and contact
 Pr Damien HUGLO
 Tel : +33 3 20 44 67 93 / Fax : +33 + 20 44 47 88
 [email protected]
Contact
 Faculty of Medicine, Research sector, University of Lille 2, 1 place of
Verdun, 59000 Lille
Key figures / Key features
The in vivo Imaging facility is one of facilities of the Institute for Predictive Medicine and Therapeutic Research
(IMPRT) created in 2000 and accredited as a Federative Research Institute (IFR 114) in 2002. This facility includes
a platform dedicated for animals and especially for small animals.
Team involved in ONCO Lille






IFR 114, IMPRT, in vivo imaging platform, small animals (Pr Damien Huglo)
IFR 114 IMPRT University Hospital Experimental Research (Dr Thomas Hubert)
INSERM U703 "interventional therapies Assisted by Image and Simulation" (Dr Serge Mordon)
Urology Department, University Hospital Lille (Pr Arnaud Villers)
Radiology and Medical Imaging Department, , University Hospital Lille (Pr Laurent Lemaitre, Dr Philippe Puech)
Nuclear Medicine Department, , University Hospital Lille (Pr Damien Huglo)
Description (skills & resources)
 a 0.2T MRI machine dedicated to the investigation of large animal models (AIRIS Mate 0.2 T MR Scanner
(Hitachi) specially pig and sheep with a special focus to MR interventional procedures
 a 7.0T/20 cm horizontal magnet MRI system for the investigation of rodent models (Biospec, Bruker, Ettlingen,
Germany), with a gradient slope of 400mT/m. For brain imaging, two separate radiofrequency coils are used :
one Bruker 72mm inner diameter volumic emitting coil which the animal bed is inserted and one Bruker
surface reception positioned to the top of the animal skull. For body imaging, only one coil allows the emission
on reception of signal.
 a preclinical PET/CT (Inveon multimodality, Siemens Molecular Solutions, Knoxville, USA) for rodents. The
maximum field of view (FOV) is 5.5 cm x 8.4 cm for CT and its theoretical maximum special resolution of 30
µm. The PET is based on LSO elements (25,600) and 64 detector blocks. The detector diameter is 16.1 cm and
the transaxial active FOV equal to 10 cm. The resolution at centre of FOV is less than 1.4 mm.
Main assets for ONCO Lille
This in vivo Imaging facility is not dedicated for oncology but perfectly suited for this and particularly in the field
of resistance and relapse. Some studies were already performed for evaluated new minimally invasive therapies,
laser interstitial thermotherapy (LITT) and photodynamic therapy (PDT) locally developed. For this, the rat
prostate cancer model was used (with MRI and fluorocholine-for PET/CT) but this can be extended in other animal
cancer models or other radiopharmaceuticals (FDG,…) and different studies are planned with different tumour
models (melanoma…).
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Academic Radiotherapy Department – Centre Oscar Lambret
Management and contact
Pr E. Lartigau, MD, PhD
 Tel: +33 3 20 29 55 95
 [email protected]
Location
 Centre Oscar Lambret, 3 rue Combemale, 59 000, Lille
Key figures / Key features
The Academic radiation Oncology department is one of the largest in France, implementing routine IMRT
techniques and stereotactic brain and body treatments. Each year, more than 3000 patients are treated on the
various machines and 550 brachytherapy procedures are performed. Contacts are ongoing with proton
manufacturers (Still River, IBa…) to set up a proton facility within 5 to 7 years. It is the European training Centre
for Accuray Inc. (Tomotherapy & CyberKnife).
Team involved in ONCO Lille
Physicians: Pr E Lartigau, Pr P Nickers, Dr X Mirabel, Dr L Schiappacasse, Dr B Coche-Dequéant, Dr B Prevost.
Physicists : T Lacornerie, T Sarrazin, N Reynaert, A Wagner, F Dubus, N Crop
Description (skills & resources)







CyberKnife, Tomotherapy Hi Art (2), Primus, Clinac 23X (2)
Leksell gamma knife
Simulation : Oldelft Simulix, Toshiba Aquilon
MRI : General Electric 3T
R&V :Nucletron Visir 2.0
Techniques :TBI, brain and body stereotaxy, multimodal fusion, gating
Brachytherapy :LDR, PDR (3), HDR, Iodine 125
Main assets for ONCO Lille
Radiation Oncology plays a key role in loco regional treatments combined to surgery and /or chemotherapytarget treatments. The development of new models (IMRT, sterotaxy) has been largely implemented, making the
Department able to cover all patient needs in the fields of daily treatments and clinical research.
Specific programs are planned in ONCO Lille project around adaptive radiotherapy in Head and Neck and
Gynaecological tumours and the development of Monte Carlo algorithms for dosimetry.
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II.3.4. INTEGRATED PLATFORM 3: ANIMAL MODELS
Four sites are collaborating in the animal model platform of the SIRIC:
IMPRT experimental animal resources platform
Tumour model platform of Institut Pasteur
Oncovet (see chapter I.2, page 30)
O.C.R. (Oncovet Clinical Research)
Each site complements other‟s activities in terms of studied animals (experimental animals,
including genetically modified mouse models vs. pets from private owners), tumour models
(induced vs. spontaneous) and available resources (personnel, scientific expertise, imaging and
treatment facilities on genetically modified mouse models).
Regarding first scientific program on tumour and host-resistance to loco-regional treatments, a
surgical suite and radiation therapy unit are available at Oncovet for loco-regional treatments of
cancers. A specifically dedicated team of veterinary specialists will provide standard of care
treatment to dogs with spontaneously arising cancers. Along with previously published datas
regarding response to treatment and tumour and host related resistance, this highly skilled team
will provide additional data and tissue samples for the identification of key factors identified in
both other models and human tumours. O.C.R. tumour tissue bank will be open to experimental
animal facilities to study tumours that have failed to respond to loco-regional treatment in
canine patients. The main connection is to investigate and identify physio-pathological
processes in experimental rodents then subsequently confirms that these mechanisms occur in
dogs spontaneously affected by cancers. Tumour tissue bank gathered in dogs could be used
for the establishment of xenograft models of canine tumours in mice, for experimental validation
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of canine models. For this evaluation, experimental and clinical structure will share their common
resources (with complete technical structure for both diagnostic imaging and treatment) and
expertise, for the selection of the most relevant models. The Institut Pasteur structure could then
established mice model of tumour xenograft from tissue bank gathered in dogs. Evaluation of
therapeutic candidate in xenograft model could be later translated to spontaneous tumour in
dogs, in order to propose a more pertinent model of spontaneously occurring tumour for
preclinical evaluation of diagnostic and therapeutic candidates. The clinical evaluation will be
performed in Oncovet but will be supervised by OCR (with specifically dedicated team skilled in
monitoring veterinary studies), to propose a methodological and technical supervision similar to
clinical phase 1 and 2 study. Datas emerging from these studies will therefore be of high scientific
value (as highly pertinent and validated models will be used) and will be ethically indisputable
(as animal with spontaneously arising tumours will be treated with standards of care and
innovative therapeutics procedures).
Regarding second scientific program on tumour dormancy and immunoevasion, available
mouse and dog models will be shared to identify the most relevant model for each tumour type.
Tumour dormancy biomarkers will be identified in either of the previous models then validated in
the other model. The main connection is to evaluate candidate drug efficacy on tumour
dormancy in pre-clinical rodent model then establish proof-of-concept via clinical studies in
dogs spontaneously affected by cancers. Again, data of high scientific value could be
gathered at the Oncovet centre thanks to the methodological an technical support of OCR.
These studies will bring valuables data on both efficiency and long and short-term toxicity of
candidate therapeutic products proposed.
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Preclinical rodent tumour models : IMPRT and Institut Pasteur de Lille
Two equipments for animal housing
Researchers have access to two equipements of animal housing which are operational and in close connection.
 The first is located in the CHRU site within the IMPRT
 The second is on the Pasteur Campus, close to the Institut de Biologie de Lille.
Common teaching user sessions are organized: one session per year for legal training in animal care level 1 and 2.
The IMPRT platform is completed with an effective tray of animal imaging.
These facilities are accessible to all teams of the Lille scientific community.
Skills and resources of both facilities are described in the two following sheets
Team involved in ONCO Lille, for both equipments
Inserm U837 (Team 3, 4 and 5), UMR 8161 CNRS, Inserm U1003
Main assets for ONCO Lille
 A highly-qualified Staff (A Scientific Supervisor in charge of the management of the platform and a technician
devoted to histological techniques). All the staff members have the full legal capacity in animal care and
training in surgery.
 Open access
 Non-routine procedures, Protocol development
 Access to a catalogue of models
 Offers a service to researchers to perform customised projects
 Derivation of lines, the maintenance of lines under SPF conditions
 Histopathological analyses
These platforms will be useful tools in the framework of ONCO Lille projects:
 Tumour and host resistance to loco-regional treatments IP-1 & 2:To study response to loco-regional
treatments in spontaneous and induced animal models in developing animal models to determine physiopathological processes linked to primary or secondary tumour resistance (oesophageal cancer)
 Tumour dormancy and immunoevasion with mouse model of tumour dormancy (Acute Myeloid Leukaemia),
Tumour stem cells (prostate melanoma) and Tumour dormancy and senescence
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IMPRT - Experimental animal resources platform
Management and contact
Thomas Hubert
+33 (0)3 20 62 34 63
[email protected]
Location
 IMPRT, IFR 114, Place de Verdun, 59045 Lille cedex
Description (skills and resources)
Equipment
 Animal facility of the University-Hospital experimental resources department, director: Thomas Hubert:
- Certification status: animals in open cages.
- Large mammals (pigs, ewes), rodents (mice, rats), Lagomorpha (rabbits)
- Available: operating rooms, micro-surgery station
 High-tech animal facility (manager Delphine Taillieu, [email protected])
- SPF (specific pathogen free) status.
- To maintain this status, animals are housed in cages individually ventilated, enabling transgenic and
immunodeficient animals to be used.
 Several areas:
- Isolation techniques: to maintain nuclei of transgenic lines under elevated confinement
- Breeding: to amplify reproducers and supply animals requested by users
- Experimentation: to cage animals included in a protocol. Among the rooms available are: stereotaxis,
metabolic studies, surgery, infusion/fixation, etc.
- A2: to infect animals with pathogens
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Tumour model platform - Pasteur Institute of Lille
Management and contact
Decavel Jean-Pierre
+33 (0)3 20 87 79 50
[email protected]
Location
PHOTOPHOTO
 Institut Pasteur de Lille, 1 rue du Pr Calmette 59000Llille
Description (skills & resources)
Animal resources
 Mouse Embryo development
- Provide mouse embryos at different stages between E 8.5 and D 3 after birth
- Provide embryo tissues at different stages
 Transgenic Models
- Related to Mouse Development
- Related to Cancer and Tumour Development
 Cancer Models
- Tumour graft
- Tumour growth evaluation
- Metastases development and evaluation
- Mammary gland development
- Mammary gland fat pad clearing
The Animal Models Core Facility can provide access to core equipment and facilities as well as expertise for
surgery or protocol development.
Equipment
 Animal surgery
- Surgical stereo-dissecting microscope
- Inhalant anaesthesia delivering system
- Alzet mini-pumps implantation
- Implantation of tumour or normal cells in mammary fat pad
- Tissues collection
 Tissue preparation and histology Animal perfusion
- Tissue collection
- Paraffin embedding unit
- Microtome
- Cryostat
- Slides staining
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ONCOVET CLINICAL RESEARCH
Management and contact
Dr Dominique. TIERNY – Director
Dr I. Bemelmans, +33 (0)3 20 56 82 93
http://www.oncovet-clinical-research.com
Location
 Immeuble ONCOVET, Av Paul Langevin, 59650 Villeneuve d’Ascq
Key figures / Key features
Oncovet Clinical Research (O.C.R.) is a private Contract Research Organization. Our objective is to propose
validated animal models of spontaneous diseases. Recent medicine history highlighted the parallel between
animal and human medicines. Pets and humans share common diseases with analog physiopathology. The
private-owned dog can stand for a relevant model for various cancers: renal, cardiac or Central nervous System
diseases. Founded in 2010, O.C.R. is a start-up with the “Jeune Entreprise Innovante” Label. The team is formed
by 8 qualified experts including 2 PhDs.
Team involved in ONCO Lille
D. Tierny, A. Hidalgo, F. Serres, C. Robat, N. Granger, I. Bemelmans, C. Delcourte, L. Fanchon
Description (skills & resources)
O.C.R. is specialized in the design, organisation, monitoring and reporting of GCP clinical studies on animals. More
specifically:
 Clinical science: O.C.R. has internal experts in oncology to select relevant animal models and define
appropriate study designs according to best practices.
 Regulatory: O.C.R. handles directly clinical trial dossier submission and interactions with French authorities
(ANSES)
 Clinical operations: O.C.R. manages the Clinical Record Form conception, investigator training, site monitoring,
data review, statistical analyses and final study report writing
O.C.R. has internal R&D programs focused on the validation of animal models. Fully validated models include:
spinal cord injury, degenerative mitral valve disease, mammary tumours and melanomas. Internal laboratory
capacities are available: histology, immunohistochemistry (IHC) managed by a certified pathologist. For oncology
projects, tumours are collected, analysed and stored in a tissue bank to later identified specific targets of interest.
A PhD project, in collaboration with IRCL (INSERM 837) started in 2011 on tumour dormancy.
Team members :
 Dr Dominique Tierny (DVM) is CEO and co-founder. She has more than 15 years of experience in clinical
oncology. She acts as a project leader and scientific advisor in oncology.
 Dr Antoine Hidalgo (DVM, MS) is Business developer and co-founder. He is a veterinary surgeon specialized in
oncologic surgery. He acts as a scientific advisor in surgery.
 Dr François Serres (DVM) is scientific advisor and co-founder. He is specialized in internal medicine and
cardiology.. He is responsible for the identification and characterization of new relevant animal models.
 Dr Ingrid Bemelmans (DVM, MS) is specialized in anatomic pathology. She previously worked in comparative
pathology in the field of mammary tumours. She is responsible for model development and target
identification.
 Dr Cécilia Robat (DVM, Dip. ACVIM-Oncology) is a specialized oncologist. She worked in medical and
comparative oncology at the University of Madison, WI. She acts as a scientific advisor in oncology.
 Dr Nicolas Granger (DVM, MRCVS, Dip. ECVN) is a specialized neurologist. He has 10 years of experience in
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clinical and experimental neurology. He acts as a scientific advisor in neurology.
 Dr Laurent Fanchon (DVM, PhD) is Head of Clinical Research and Regulatory Manager. He previously worked
for animal health company where he conducted field trials in France and Europe.
 Claire Delcoutre (MS, PhD student) is a PhD student and Clinical Research Associate. She started a PhD in 2011
on metastatic process and tumour dormancy.
Main assets for ONCO Lille
 Strong expertise in oncology: Dr D. Tierny has more than 15 years of experience and Dr C. Robat is a certified
specialist in Oncology. Both of them have a clear interest in comparative oncology. Dr Bemelmans is a certified
pathologist with a strong focus on mammary (breast) tumours.
 Large access to animals with spontaneous (non-induced) tumours: animals and humans share the same
environment, risk factors, and associated diseases
 State of the art analytic platform: OCR has internal histological platform with a ventilated table for gross
examination and formalin fixed tissue trimming; a microtome for paraffin-embedded tissue sectioning; and a
Ventana automated stainer (Discovery XT) for immunohistochemical analysis using antibodies and
immunohistochemical protocols especially adapted to canine and feline tissues. Tissue processing, paraffin
embedding, sectioning and staining are outsourced with a private human pathology laboratory (Centre
Nordpathologie).
 Canine and feline tissue bank: after phenotypical analysis of tissues samples, OCR collects frozen tissue
samples for molecular analysis relating to DNA, RNA and proteins. Tumour tissue, blood and when possible
healthy tissues of the same animal are stored at -80°C.
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II.3.5. INTEGRATED PLATFORM 4: CLINICAL RESEARCH AND METHODOLOGY
The aim of the Clinical Research and Methodology Platform is to accompany the project
participants (scientific programs and/or other platforms) from the conception phase of the
scientific project to the analysis and publication phases. To arrive at these goals, the platform
comprises units which cover all the aspects of translational and biomedical research:
2 Methodology and Biostatistics Units (MBU), one in the CHRU, another in the Centre O.
Lambret. These 2 units provide methodological aid in the planning stage of the projects
(experimental designs, primary endpoints…) as well as assistance in the statistical analysis of
the data and the publication of results. Moreover, they develop, via the framework of the
EA2694 research team, their own research topics within ONCO Lille presented below.
2 Clinical Research Units, one in the CHRU and one in the COL, united together within the
Clinical Research Centre (CRC) which is dedicated to the management of trials aiming to
facilitate and accelerate the implementation of clinical research in accordance with Good
Clinical Practice and regulatory issues.
1 unit dedicated to database-management, using professional tools and staff
1 unit dedicated to the management of registries (imperative in the research programs).
Methodology
MBU
(CHU)
MBU
(COL)
Investigation, GCP, …
FRC
See sheets n°1 & 2
UIRC
(CHU)
EA 2694
Data-management & Registries
(COL)
DPC
CR
CRC
See sheets n°3 & 4
See sheets n°5 &6
The 4 research axes of the Methodology and Biostatistics Units are the following:
1. Phase I clinical trial methodology for better patient selection and increased treatment
efficiency: Better patient selection is crucial to treatment development since results will
determine the best dose for future patients, especially in combination trials. Prognostic models
using classification and regression tree (CART) approaches for predicting the risk of early death
will be developed and implemented in trials so as to jeopardize neither the trial nor the future
drug development process. In order to estimate both long-term tolerability and anti-tumour drug
activity, the use of expanded cohorts in phase I trials is useful for evaluating the dynamics of
tumour growth. This criterion will be defined on the basis of retrospective analyses of patients
treated in different French Centres.
2. Phase II / III clinical trial methodology for optimizing treatment using criteria combining both
efficacy and toxicity: Best treatment strategy decisions rely on efficacy and toxicity, yet these
criteria are usually evaluated separately. This analysis is not optimal since it ignores competing
risks. Statistical modelling for evaluating the joint distribution of safety and efficacy outcomes will
be undertaken. A multi-dimensional parameter model including a weighted combination of
toxicity and efficacy outcomes and the doses at which one, none or both occur will be
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developed. Simulations under different scenarios and weight functions will allow a comparison of
different treatment strategies, especially for the evaluation of targeted therapy. Particular
emphasis will be on multiparametric models in these specific cancers evaluating different
endpoints such as survival adjusted for quality of life, incorporating human sciences parameters.
3. Developing innovative prognostic scoring systems applicable to optimisation of treatment
strategies and followup: Prognostic scoring systems are now widely used for evaluating the
severity of the disease before many treatment decisions. The EA2694 team has a strong
experience in the development of state of the art prognostic scores in haematology
(Waldenström, Acute Myeloid Leukaemia, Primary Myelofibrosis). We will develop similar scoring
systems in other malignancies such as prostate, oesophagus and head and neck carcinomas
with the aim to identify primary to the initiation of treatment, patients who will likely present
features of chemoresistance or tumour dormancy. Another objective is to design prognostic
models applicable during the follow-up of patients for predicting the risk of subsequent
competing risks, taking initial and follow-up characteristics into account.
4. Developing new methods of “scan statistics” in order to identify clusters of excess or low
cancer incidence: Detection of atypical geographical areas in terms of cancer incidence is an
important problem in epidemiology of cancer disease. The aim of Scan statistic methods is to
detect temporal and spatial clusters wherein the risk of cancer is higher (or lower) than in the rest
of the studied area by using data from registries. EA2694 has been working for several years in
this domain and we propose to apply this methodology in order to identify clusters of excessincidence or low-incidence of cancers in this project. In addition, we will develop original
research in the field of scan statistics: (1) estimation of the scan statistics distribution; (2) error
estimation in the p-value approximations; (3) assessment of the influence of the window frame
on the approximation of the scan statistics distribution.
Regarding the Clinical Research Units, the CRC is based on the following
"a single acces" for training in the use of administrative records, regulatory and logistical
aspects for clinical trials taking place in the Lille site.
a common functional platform for investigation and treatment of early phase trials involving
the investigators, clinical research assistants CRA and nurses.
CRC organization includes:
Regular updates of GCP knowledge for all the investigators
Consultations with an expert clinical research nurse before each inclusion
Specific communication to the Genaral Practitioner to inform him/her of the trial objectives
and potential treatment side effects
Guarntee to the patients a privileged access to the common platform of molecular biology
and imaging platform and functional imaging
Provide to the clinical research organizations (CRO), academic cooperative groups and
industrial partners involved, an active solicitation for access to early phase trials
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Methodology and Biostatistics Unit - CHRU
Management and contact
Pr. Alain Duhamel – PU-PH, Director of MBU
+33 3 20 44 55 18,
[email protected]
Location
 CHRU Lille, EA2694 - University of Lille 2, 1, Av O. Lambret - 59800 Lille
Key figures / Key features
The Methodology and Biostatistics Unit (MBU) of the Lille Universitary Hospital (CHRU) is a dedicated platform for
the methodological and statistical aspects of research projects. It includes 6 biostatisticians, 1 Data manager, 2
epidemiologists and 1 assistant professor in Medical Informatics.
MBU takes in charge every year nearly 70 new clinical research projects in the frame of this main activities :
 the development of clinical research projects (design, objectives, primary endpoint, sample size, statistical
analysis plan),
 the data management of clinical databases, statistical analysis and the interpretation of results (statistical
modeling, survival analysis, development of prognosis scores)
 the participation to scientific publications.
The Unit of Methodology and Biostatistics builds on skills of the research team EA2694 – "Public Health:
Epidemiology and Quality of Care", which focuses on three topics:
 Quality of care and methodologies in the fields of Biostatistics,
 Medical Informatics and Health Economics,
 Epidemiology of chronic diseases.
EA2694 gathers 34 researchers, 7 engineers and 13 PHD students: epidemiologists, clinicians, and methodologists
in the fields of biostatistics, medical informatics and health economics. Ranked A by the AERES in 2009, EA2694
has published 580 publications in international journals since 2000. Directed by Pr Alain Duhamel (index H= 32), it
is the lead team for the PSIP project funded by the FP7 (2008-2011) and has obtained 5 grants from ANR and 6
PHRC (French Ministery of Health).
Team involved in ONCO Lille
The principal investigators involved in ONCO Lille will be A Duhamel (Professor of Biostatistics PU-PH), managing
the EA2694 team and the MBU, and working in the field of high dimensional analysis, knowledge data discovery
from large databases and development of prognostic scores. He will be assisted by :
 G Marot, assistant professor in biostatistics and expert in the interpretation of genomic data analysis using
high dimensional analysis.
 F Vasseur, assistant professor specialist in genetic epidemiology.
 M Genin, doctoral scientist in the field of scan statistics for the detection of clusters of events.
The engineers of the MBU (P Devos, J Salleron, S Pesin) will participate in the clinical studies developed in ONCO
Lille for the design, the data management and the statistical methodology.
Description (skills & resources)
EA2694 and MBU have developed major advances in biostatistics concerning high dimensional analysis for
longitudinal studies or genomic data, development of diagnostic or prognostic scores, scan statistics for the
detection of clusters of events, handling of missing data and data mining techniques for the analysis of large data
bases. Recently, the team has recruited a researcher specialized in cost effectiveness analysis which will
contribute to ONCO Lille.
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The expertise of EA2694 and MBU in the field of clinical/translational research (study design, data management,
statistical analysis, scores development) is well-established. The team's members are strongly involved in clinical
research at the Lille universitary hospital and they work with all clinical teams on the site, notably with
oncologists, paediatricians, pneumologists and ICU physicians.
All members of the MBU are equipped with especially dedicated hardware and software (SAS, Stata, R, Capture
System ...) necessary for the conduct of research projects.
The members of MBU have coauthored 287 publications in international journals since 2007 including papers in
the New England Journal of Medicine, Lancet, Blood, CMAJ, Radiology, Gastroenterology, Critical Care Medicine,
Neurology and J Clin Endocrinol Metab.
Main assets for ONCO Lille
The Methodology and Biostatistics Unit and the team EA2694 will participate in the clinical researches studies
developed within ONCO Lille via the “Methodology and Clinical Research” platform :
 clinical validation of new biomarkers (biomarkers for the early diagnosis, biomarkers of severity of disease,
predictive biomarkers of the disease evolution),
 development of prognostic scores,
 development and assessment of new drugs,
 epidemiology of cancer diseases,
 identification of spatial and space-time variations in incidence of cancers using scan statistics.
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Methodology and Biostatistics Unit (COL)
Management and contact
Andrew Kramar – Biostatistical director
 Tel: +33 3 20 29 58 93
 [email protected]
Location
 Centre Oscar Lambret, Lille
Key figures / Key features
Key features concern research areas in bio statistical and computational issues that arise in the design, analysis
and statistical modelling of clinical and preclinical studies. Methodological research concentrates on models for
efficient designs for evaluating efficacy and safety endpoints in early phase clinical trials, especially combinations
of cytotoxic and biological agents and radiotherapy. Analyses of recurrent and transient side effects of varying
severity, with a special attention to radiotherapy late effects, is of particular interest as is quality of life and the
modelling of multiple biomarkers as longitudinal data for the monitoring of response to treatment within a
competing risks framework. The statistical challenges to multidimensionality problems of microarray analyses are
another important research theme.
Dr A. Kramar (H-index=30) has published 141 articles (36 since 2007, 41 as first or last author) covering many
aspects of cancer research. About 30 statistical studies have been conducted within the past 5 years.
Team involved in ONCO Lille





EA 2694: translational and fundamental research
MBU CHRU: study design, data analysis and publication of clinical trial results
UIRC / FRC: regulatory, logistic, financial and organisational aspects of clinical trials
Persons participating in the project:
COL: Two research biostatisticians (PhD), two statisticians (MSc), 2 data-managers, and 1 data entry
technician.
Description (skills & resources)
All members of the unit are equipped with especially dedicated hardware and software (Clinsight, SAS, Stata, R,…)
necessary for the conduct of research projects. Skills involve expertise in cancer clinical trials and biostatistics. A
400 page book co-authored by Dr A. Kramar entitled “Méthodes biostatistiques appliquées à la recherche clinique
en cancérologie” has recently been published (Nov 2011), and reflects the large number of domains using
statistical methods in cancer research.
Main assets for ONCO Lille
A close coordination with the Clinical Research Unit, especially academic sponsored trials as well as a coordinated
accompaniment and a direct implication with the teams involved in the main programs and platforms of ONCO
Lille. Regular training of young statisticians and researchers allows an organisation of scientific meetings on
statistical methods around common problems, especially new methodological developments.
A guarantee that a well designed, well conducted and correctly analyzed research project will have a high impact
in the scientific community as opposed to a poorly designed and incorrectly analyzed project which will not be
convincing, will have a low impact and wasted resources both financial and medical.
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Clinical Research Unit of the CHRU – Federation of clinical research
Management and contact
Christian Libersa, MD/PhD, Director of “Fédération de
Recherche Clinique”, CHRU de Lille
 [email protected]
 tel: 0033. 3. 20.44.41.45
Location

Bat USN B, Centre Hospitalier Régional, 59800 Lille
Key figures / Key features
The « CHRU de Lille” has since fifteen years initiated a process to support translational research by creating a
"Delegation to Clinical Research and Innovation "(DRCI) covering all aspects of biomedical research. In 2006, it
created the Federation of Clinical Research (FRC) responsible of (1) the instruction and assistance in the
preparation of clinical research projects sponsored by the establishment (2) the operational implementation of
clinical research projects (academic and industrial) and their follow-up.
Those activities are performed by specialized clinical research professionals in structures or platforms which
support the investigation (CIC, CRB…). It provides analytical support, methodological support (in relation with
the MBU) and logistical support and management of regulatory issues. It provides investigators the resources
(Clinical Research Technicians) required for the investigational activity for the daily conduct of clinical studies.
Concerning Oncology, the “CHRU de Lille” sponsored in 2010 24 studies (with 428 patients included in our
establishment), was investigation centre in 298 studies (159 academic studies and 139 industrial studies) with
685 patients recruited.
Team involved in ONCO Lille




The Federation of Clinical Research
The Clinical Investigation Centre: structure labelled by INSERM and dedicated in early phases
The Biological Resource Centre: structure dedicated to the management of samples and biological collections
The Technology Investigation Centre: structure labelled by INSERM and dedicated in evaluation of medical devices.
Description (skills & resources)
The Federation of Clinical Research includes medical resources, administrative resources (secretaries,
assistants...) and specialized resources in clinical research:
 About 10 full-time clinical research associates (CRA)
 About 70 full-time technicians of clinical research (TCR)
 About 2.5 full-time about pharmacovigilance and quality assurance.
These resources are changing depending on the number of projects undertaken within the institution.
Currently, nearly 20 CRA/TCR are dedicated to research activity in Oncology, especially in haematology,
digestive surgery or respiratory oncology.
Main assets for ONCO Lille
The Federation of Clinical Research has proven expertise in managing clinical trials (high annual number of
projects), including oncology.
As part of the project SIRIC, it will allow:
 The guarantee of quality clinical research
 A very useful assistance in the process of translational research
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Clinical Research Integrated Unit (UIRC) - COL
Management & contact
Stéphanie CLISANT, PhD,
[email protected]
tel: 00 33.20.29.55.60
Location
 Unité Intégrée de Recherche Clinique, 3 rue F. Combemale,
59020 Lille
Key figures / Key features
The clinical research integrated Unit (UIRC) of the COL is dedicated to the management of trial aiming to
facilitate and accelerate the implementation of clinical research in accordance with Good Clinical
Practices.Since 2007, the Centre Oscar Lambret is one of the top five in terms of number of patients included
in clinical research and one of the top 3 in terms of trials sponsorship among the French cancer centres.
706 patients were included in 158 clinical trials, representing more than 12% of active file of patients in 2010.
Interestingly, the part of academic trials represents more than 80% of included patients. Studies conducted
are principally phase I, II and III therapeutic studies of new molecules or therapeutic strategies with a
particular focus on translational research. More than 20 trials are sponsored by the COL each year, recruiting
500 patients all over the country
The development of these projects is carried out with the support of the Methodology and Biostatistics Unit
st
of the Centre, under the direction of Andrew Kramar since April 1 2010.
Team involved in ONCO Lille
The UIRC is divided into 2 sub-units: the first one is dedicated to management of investigational protocol
sponsored by pharmaceutical industry and academic groups. The second one is dedicated to sponsoring
activity. It provides methodological support, regulatory and logistic documentation for the development of
projects planned by investigators of the Centre. As such, it centralises and also sponsors projects susceptible
to enter into the scope of grant proposals from INCa (Institut National du Cancer), notably the PHRC and
pharmaceutical industries.
Description (skills & resources)
The UIRC disposes of a care unit with 8 beds and medical chairs specifically dedicated to taking care of adult
cancer patients included in early phase clinical trials (phase 0, 1 or 2). The unit was conceived as an
interdisciplinary platform dedicated to clinical and translational research.
The staff of the investigation unit includes 3 full-time CRA and 7 full-time TRC (Clinical Research Technicians).
Each CRA and each TRC is in charge of one or two cancer sites. One ARC is responsible for applying quality
control procedures.
The sponsorship unit comprises 2 ARC project leader and 2 ARC monitor and an assistant administrative trial manager.
The projects are managed and conducted by a single organisation allowing a rapid implementation of the
study (mean delay of 2 weeks after receipt of the CPP (Comités de Protection des Personnes) and AFSSAPS
(Agence Française de Sécurité Sanitaire des Produits de Santé) authorisations, once the internal
authorisations of the CEC (Commission des Etudes Cliniques) of the Centre have been obtained. This
commission meets monthly and insures the scientific importance of each study in accordance with the
strategic and political orientations of the Centre and its external scientific council. If necessary, extraordinary
meetings of the CEC can be organised for rapid decisions depending on the importance of the proposed study.
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Main assets for ONCO Lille
Among all projects sponsored by the UIRC, a certain number already concern the pathologies mentioned by
ONCO Lille:
 Rational pharmacological individual adaptation of doses of pemetrexed (Alimta) administered with
cisplatin and vitamin supplementation in patients with a pleural mesothelioma
 Morphological and molecular characterisation of head and neck tumour occurring in patients who have no
risk factors for alcohol or tobacco or professional
 Stereotactic irradiation for hepatocellular carcinoma: Phase II study
 A multicentre randomized phase II study to evaluate the benefit of chemotherapy plus best supportive
care (BSC) versus BSC in patients with metastatic oesophageal cancer (MOEC) of squamous-cell type (SC)
(MOEC-SC) who have not experienced disease progression or unacceptable toxicity during a 2 monthcourse of chemotherapy
The Unit will be an important platform for the development of new investigational projects and sponsored
projects in the fields of ONCO Lille:
Furthermore, 4 projects are conducted in collaboration with the University of Lille 3 (Dr Véronique
CHRISTOPHE), who convinced us of the importance to pursue and amplify this research in behavioural science
coupled with clinical trials
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Canceropôle Nord Ouest Data Processing Centre (DPC)
Management and contact
Michel Henry Amar, MD, PhD
+33 231 455093
[email protected]
Location
 Canceropôle Nord Ouest, 2, avenue O. Lambret, 59000 Lille
Key figures / Key features
The DPC conducts studies for (i) projects that have been assessed and funded by institutional organisations,
funding agencies or charitable scientific organisations and foundations, and (ii) projects promoted and/or
funded by the three comprehensive cancer centres in the four-region group, or by the scientific cooperation
group run by the four university hospitals (insofar as they are part of a clear effort to structure research in the
four-region group). Research projects focus on phase II and III clinical trials and on diagnostic, prognostic and
epidemiological studies promoted by institutional organisations.
Team involved in ONCO Lille
The DPC team is composed of 1 director, epidemiologist, specialized in public health; 1 project leader, chemist;
1 biostatistician; 2 data managers; and 1 data operator (data entry and data processing). All of them are taking
part in ONCO Lille.
Description (skills & resources)
The DPC team offers skills in data management of health data that concern clinical trials, diagnostic and
prognostic studies as well as epidemiological studies. They can also provide advice and assistance in the study
design, logistics, statistical analysis and publication of results.
Resources include on-line data base management software which complies with the EMEA/FDA requirements
regarding IT systems as well as electronic signature and various international norms. It can be accessed by
authorized people through a highly secured system (VPN/SSL mode up to 128 bits; Transmitted data
encrypted). Its web interface allows study management via standard data entry in client/server and/or via the
Internet. Daily backup is made using two independent servers. Resources also include standard statistical and
graphical software facilities.
The DPC was certified by the French National Cancer Institute (INCa) in July 2007.
Main assets for ONCO Lille
The DPC represents an essential strategic and logistical tool in the development and the management of clinical
and epidemiological studies to be sponsored and conducted within the SIRIC framework.
The DPC can also be viewed as an opportunity for joint projects involving research teams in biology, humanities
and social sciences and clinic.
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Cancer register of Lille and its area
Management and contact
Dr Karine Ligier - Scientific coordinator
 [email protected] / 0033 20 97 94 92
Location
 Registre général des cancers de Lille et de sa région (GRPS/CRRC) 235
avenue de la Recherche - 59373 Loos cedex
Key figures / Key features
The General Cancer Registry of Lille and its area was formally created in January 2009, and is integrated in the
Regional Cancer Reference Centre Healthcare Cooperation Group (GCS – C2RC). Certified by the National
Committee of Registries (InVS and Inserm) since November 2008, its missions are to:
 Produce local cancer statistics, and participate in the production of regional cancer statistics, national and
international
 Assess the impact of public health measures
 Develop studies on the care management of patients
 Develop ethological studies on the determinants of the occurrence of cancer or the care management and
survival of patients.
The registry records the following tumours in the area of Lille (800 000 inhabitants):
 invasive cancers
 in situ cancers of the colon-rectum, breast, cervical, melanoma
 ovarian tumours "borderline"
 tumours benign or of uncertain for the bladder and central nervous system.
The data are collected from 35 sources (pathology and biology laboratories, hospital, health insurance…)
Team involved in ONCO Lille
The team is composed of a chief scientist two epidemiologists and investigators, a data manager, five clinical
research assistants and a secretary, who will participate to the SIRIC project
Description (skills & resources)
Currently, the General Cancer Registry of Lille (800,000 inhabitants) is collecting data on patient ages and
addresses, incidence dates, and cancer topography, morphology, and size. Incidence data for 2005 and 2008
are available on the website of the registry: www.registrecancers59.fr. These data show that there is strong
excess- incidence of cancers related to tobacco +/- alcohol (UADT, oesophagus, lung, and bladder) compared to
the national incidence.
Some medical data, such as the stage of cancer at diagnosis or the modality of diagnosis could be collected. So,
we manage or participate in epidemiological research concerning descriptive epidemiology of care
management and survival of patients with head and neck cancers, prostate cancers and patients with sarcoma.
Main assets for ONCO Lille
Thus, additional surveys will be conducted to supplement the information already collected by the Registry. For
this purpose, field-specific studies (epidemiology, biology, genetic, psychology, informational sciences,
economic…) will help to explore occurrence, management care, late diagnosis and survival of patient with
cancer issued of the general population (i.e. unbiased recruitment).
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III.
Integrated research programs
III.1. Overview of the two integrated programs
ONCO Lille will develop an original project aiming to achieve state of the art integrated
research in some of the most important issues for oncology: tumour resistance and persistence
after loco-regional treatments.
ONCO Lille will develop two major programs:
Program 1 will focus on tumour and host resistance to loco regional treatments and on the
understanding of late diagnosis and socio economical resistances to enter medical care.
Program 2 will be dedicated to tumour dormancy and persistence and on the modelling of
tumour recurrence and patients reinsertion
Program 1 will have a primary objective to identify the key-determinants for resistance to locoregional treatments. For this, 5 research axes are proposed:
1- To identify cell determinants and signalling pathways involved in resistance in order to
develop new biomarkers and dedicated targets
2- To evaluate new imaging tools for early diagnosis and follow-up after loco-regional
treatments
3- To study response to loco-regional treatments in spontaneous and induced animal models
4- To develop diagnostic and therapeutic clinical approaches to decrease the tumour and
host trend for resistance
5- To strengthen the access to care and reduce treatment delays, that may strongly influence
host (and probably tumour) resistance
Two emerging programs will be developed (see Chap III.3.4):
To improve efficiency in loco-regional radiotherapy treatment, with the development of a
transversal Monte-Carlo dose engine
To model morbi-mortality of primary liver cancer in France across various stages of severity:
evaluation of different strategies according to the amount of screening and therapeutic
resources.
Program 2 will have a primary objective to understand recurrence. The program will specifically
focus on mechanisms contributing to tumour dormancy and relapse after a period of complete
remission. With specific goals:
1- To create new experimental models of tumour dormancy.
2- To understand basic mechanisms of tumour dormancy
3- To identify new predictive factors of relapse and translate them into the clinic
4- To develop new drugs able to target dormant tumour cells and avoid or delay relapse.
Two emerging program will be developed:
To model treatment follow up
To adapt socio professional reinsertion
Based on a large number of clinical and fundamental research programs and on the existing
level of excellence, the project has the originality to stand on very strong basic or clinical
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research and to be able to achieve significant breakthroughs in the modelling of resistance to
initial treatment and recurrence after treatment for the benefit of patients and healthcare
providers.
All programs will integrate biological research, translational research, innovative imaging, clinical
research and humans sciences developments, particularly in the field of comprehensive
handling of the disease for the patient and the family (global care). Dissemination of knowledge
will be directed towards patients in the field of adapted follow up and professional reinsertion, as
well as towards general practitioners and political authorities.
The consortium ONCO Lille will bring new data on the mechanisms of resistance and persistence
to treatment in human tumours. Bringing together such information in biological models,
imaging and clinical research will help to drive new studies in the field of adaptive and
personalised medicine. Due to the specific cancer incidence in our region, this proposal has
clinical reality. Based on the past 5 years‟ history of integrated research, together with the
involvement of all players in cancer care and strong political commitment, our project provides
a real opportunity to implement a truly comprehensive cancer centre in north of France.
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III.2. Tumour and host resistance to loco-regional treatments
Program 1 coordinator:
Pr. Christophe Mariette, MD, PhD, Clinical Department of Oncological surgery, Inserm research
team U837-E5 “Mucins, epithelial differentiation and carcinogenesis”, University Hospital of Lille
and Lille 2 University
[email protected]
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III.2.1. MAJOR THEME OF THE PROGRAM
III.2.1.1. MEDICAL RATIONALE AND SCIENTIFIC OBJECTIVES OF THE PROGRAM
Head and neck, oesophageal, gastric, primary liver, lung and mesothelioma cancers are still of
poor prognosis despite increasing efforts to optimize therapeutic strategies toward a better locoregional and systemic disease control. Despite aggressive therapeutic strategies combining
frequently, in the post and/or in the preoperative settings, surgery, chemoembolization,
radiofrequency, radiotherapy and chemotherapy, most of the treated patients will experience
persistence disease due to treatment resistance ; the causes of which are numerous and need
to be better understood.
Consequently, the researchers of this Program seek to identify key factors which are linked to
tumour and host resistance to loco-regional treatments. We propose a comprehensive
integrated research program that explores these factors using complementary approaches:
identification of biological paradigms explaining resistance, animal bearing tumour models,
modern imaging techniques explorations, and identification of social and compartemental
determinants. This integrated research will be backed onto an important activity in clinical and
surgical research dealing with the impact of loco-regional treatments for head and neck, oesogastric, primary liver, lung and mesothelioma cancers. This Program integrates experienced and
internationally known physicians (numerous grants and high level publications), high-level
researchers (A+/A AERES), and numerous industrial partnerships towards a patient-specific
diagnosis and treatment for those targeted cancers. Within this overall aim, each team brings to
this Program complementary expertise and approaches.
The primary objective of the research program is to identify the key-determinants for resistance
to loco-regional treatments. For this, 5 research axes are proposed:
1- To identify cell determinants and signalling pathways involved in resistance in order to
develop new biomarkers and dedicated targets
2- To evaluate new imaging tools for early diagnosis and follow-up after loco-regional
treatments
3- To study response to loco-regional treatments in spontaneous and induced animal models
4- To develop diagnostic and therapeutic clinical approaches to decrease the tumour and
host trend for resistance
5- To strengthen the access to care and reduce delays in the initiation of treatment, that may
strongly influence host (and probably tumour) resistance
Moreover, two emerging programs will be developed (see Chap III.3.4):
To improve efficiency in one of the loco-regional treatment, radiotherapy, with the
development of a transversal Monte-Carlo dose engine
To model the morbi-mortality of primary liver cancer in France across different stages of
severity: evaluation of different strategies according to amount of screening and therapeutic
resources.
These integrated axes will offer the possibility to reinforce the interaction between clinical,
translational and basic research with a common goal of enhancing patients‟ survival, quality of
life and quality of care. Results coming from basic and translational researches will be transferred
to clinic, as much so as data generated across clinical trials will feed the fundamental and
translational research programs.
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III.2.1.2. METHODOLOGICAL BACKGROUND
In the context of excess-incidence and mortality in the Nord-Pas de Calais region and an
incredibly high number of patients treated for these targeted cancers, clinical teams involved in
the head & neck, oeso-gastric, primary liver, lung and mesothelioma cancers have developed
numerous clinical research programs characterized by (i) a large active file of patients, (ii) a
large number of funded therapeutic trials, (iii) a national and international visibility. This on site
clinical research had as its objectives (i) to improve cancer treatment by offering a large panel
of trials dedicated to innovative strategies, (ii) to allow patients‟ access to personalized
treatment in order to decrease resistance to treatments and improve survival, (iii) to integrate
translational research programs, (iv) to rapidly integrate results from translational research to the
bedside and (v) to contribute to reducethe reduction of health inequalities.
Whatever cancer is treated, all the above pathologies are characterized by a strong affinity with
loco-regional treatment resistance. The vast majority of patients will have residual tumour tissue
after chemotherapy, radiotherapy, chemoembolization, radiofrequency, immunotherapy or
surgery, defining the tumour resistance and leading more and more to consider various
associations between those treatment options. Despite empirical associations of treatments,
knowledge of parameters that lead to predict before or during the therapeutic sequence the
resistance to such loco-regional treatment is poor. Identification of common mechanisms
sustaining chemoresistance in cancer as well as specific determinisms for each of these cancers
are urgently needed. Moreover whereas many research programs are frequently oriented to
identifying tumour factors linked to resistance, there is more and more evidence that the host
plays an important role as well.
However very little is still known (Pubmed : (Tumour resistance) AND (local treatment): 911
publications since 2006), about the underlying cellular and tumour mechanisms involved, the
respective roles of the tumour and the host in such resistance, as well as the ways to anticipate
and predict this phenomenon and the therapeutic tools necessary to fight against this fatal
event. Even if, based on the knowledge of such high level of resistance in these cancers, many
clinical trials on site have been empirically designed to define the optimal treatment strategy for
each patient and each cancer (clinical research programs, coordinator C Mariette), various
additional and complementary approaches have been initiated in order to improve the
understanding of the determinants leading to tumour resistance: identification of the underlying
cellular mechanisms and signalling pathways involved (basic research programs, coordinator Y
De Launoit), identification of the biological and genetic predictors of resistance (biology and
pathology platforms, coordinator N Porchet), modelling of spontaneous or inducible tumour
resistance in animal models (animal facilities coordinator D Tierny), imaging modalities to detect
early tumour resistance (coordinator I Fournier), conceptualizing appropriate study designs
(clinical research platforms, coordinator A Duhamel), and determine human and social
components that may impact on tumour resistance through suboptimal access to care and
treatment initiation delays (coordinator V Christophe).
The following opportunities are unique in strengthening the present program
A large local recruitment of head & neck, oeso-gastric, primary liver, lung and mesothelioma
cancers: the Lille region recruits more patients into trials dealing with each of these cancers
than any other region in France, and is one of the top 3 recruiting centres in Europe
A unique potential in France to develop such an integrated research program due to the
high specificity and visibility of the Lille region in upper GI, head and neck, mesothelioma and
primary liver and lung cancer
A dedicated research activity on these poorly studied cancers in which few academic
groups or industrial companies are emerging. In fact, industrial partnerships usually prefer to
sustain research programs issued from large specialized centres, due to well-known difficulties
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to drive programs in these cancers: patients with numerous co-morbidities, complex
diagnostic and therapeutic strategies, lower recruitment rates... This may give a strong value
to this program since (i) the probability for having another relevant integrated program on
these pathologies in France is scarce, (ii) the SIRIC label will offer a unique opportunity to
intensify research and partnerships dedicated to these cancers.
An intensive clinical research activity based on a panel of more than 400 studies per year,
including a large number of Phase I-II trials and dedicated regional or national cohort
studies driven by the C2RC (examples of available cohorts > 2000 oesophageal cancers, >
3000 gastric cancers, > 1000 liver cancers… ) (See appendix; chapter 2).
Already designed induced or spontaneous animal models dedicated to evaluate the impact
of both tumour and host factors to cancer resistance
Numerous funding from the National Cancer Institute (PAIR, PHRC, ICTs), ARC, National
League against cancer, Regional Council, Fondation pour la Recherche Medicale
Active industry-sponsored research trials (BMS, Novartis, Bayer Schering Pharma, Abbott,
Pfizer, Roche, Merck, Nestlé, GSK, Amgen, Boehringer-Ingelheim, DAichi, CosBio, Transgene,
Pierre Fabre)
Integrated clinical research units dedicated to each cancer with a central coordination
(CRC)
Comprehensive, high-technology facilities (biology, serial and functional imaging, surgery,
radiotherapy, medical oncology) and Human and Social Sciences departments
Collaborative national and international groups involved (GORTEC, GETTEC, EORTC, PRODIGE,
FFCD, FRENCH, FREGAT, IFCT, ELCWP etc.)
Regional organizations for the management of primary liver cancer (networks: CIRRTRANS,
interregional network CARNOR, S Dharancy), oesophageal cancer (OESO data base C
Mariette), lung and mesothelioma cancers (CBNPC 59-62 database A Scheerperel)
Socio-economic conditions in the region known as often unfavourable, combined with a
relatively low medical density leading to intense recourse activity.
III.2.1.3. ASSETS OF LILLE’S TEAMS
Overview
Critical mass of researchers and A+/A research teams working in the field of resistance to
loco-regional treatments: 10 teams; 30 researchers
Availability of dedicated platforms with availability of serum and tumour banking with a hot
topic on tumour resistance: 42 teams in methodology, imaging, fundameltal biology and HSS.
Available large data bases dedicated to the targeted cancers
Strong involvement of clinical researchers in programs investigating both tumour and host
factors that may lead to tumour resistance: 13 clinical researchers, 79 dedicated clinical
programs
National and international research collaborations on these cancers based on a strong
national leadership
Important contributions to local scientific structuring and networks of collaboration
partnerships linking Research in Oncology
Already strong interactions between the actors of the program‟s axes as illustrated by
numerous common publications and ongoing multidisciplinary funded programs (INCa
PHRC,STIC, ARC; Ligue contre le Cancer )
High level of scientific production and international visibility: more than 800 publications in
Oncology referenced in Medline since 2006 (cancer AND Lille[Affiliation]), more than 400
invited conferences, coordination of many national
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Partnership with regional or national scientific societies: FFCD, PRODIGE, UNICANCER, FRENCH,
SFCD, SPLF, ERS, IASLC, IMIG …
Well established clinical and translational research
Strong valorisation and translation into clinical applications : in 2010, 80 clinical trials sponsored
by the Lille University Hospital or the Cancer Centre, including 14 translational research trials
and 18 PhaseI/II trials, with more than 1300 included patients, 440 studies sponsored by
academics or industrial companies, with more than 1000 included patients (see appendices 2
and 5), partnerships with biotech (Lunginnov, CisBio International, ....) and the
pharmaceutical industry (BMS, Novartis, Bayer Schering Pharma, Abbott, Pfizer, Roche, Merck,
Nestlé, GSK, Amgen, Lilly, MSD, DAichi, Mundipharma, Eisai, IRIS/Servier, Fortis....)
Long lasting collaboration between the COL, the CHRU and platforms.
International recognition of clinician leading European networks in particular in oesogastric
cancer (C Mariette), liver determinants leading to cancer resistance (P Mathurin, S
Dharancy), tumour determinants of resistance in Head and neck (JL Lefebvre) and
mesothelioma(A Scherpereel) cancers
On going basic research and clinical trials aiming at reinforcing the host against the tumour
(immunonutrition in oesogastric cancer (Nestlé), anti MAGE A3 immunotherapy against
oesophageal tumour cells (GSK), pro-apoptotic drugs such as HDAC inhibitors in lung cancer
(ELCWP 01081 trial) or malignant pleural mesothelioma (IRIS/Servier, ELCWP 01062 trial),
immunostimulant to fight lung cancer (Talactoferrin – Fortis), Immune response to pleural
malignancies assessment and induction (academic study), pharmacogenetic and
pharmacodynamic evaluation of response to induction chemotherapy for head and neck
cancers, anti EGFR targeted therapies (monoclonal antibodies: cetuximab, panitumumab,
zalatumumab or anti-thyrosin kinase inhibitors: afatinib, lapatinib), prediction to cetuximab
infusion-related reaction, place of integrin inhibitors (cilengitide) in recurrent/metastatic
diseases, combination of cytotoxic drugs and molecular targeted therapies for larynx
preservation…
National reference centre for rare diseases such as malignant pleural mesothelioma, (Label
by the French Ministry of Health and DHOS)
Access to multiple integrated platforms (see paragraph VI.3.1)
Multiple national and scientific programs with financial supports (see appendix IV)
Partnership with different pharmas on national and international clinical trials
Sponsored by the COL, CHRU, French Intergroup of Thoracic Oncology (IFCT), European Lung
Cancer Working Party (ELCWP), Nestle, Merck, GSK, Amgen, Boehringer-Ingelheim, Lilly, Roche,
IRIS-Servier, Daichi, EISAI…
Oesogastric location
National and international trials with Nestle (Switzerland and France) for developing immunomodulating nutritional supports with the aim of enhancing immune status to increase
response to loco-regional treatment in both preclinical and clinical studies (C Mariette 2005 ongoing)
Contracts/collaboration with Meck-Serono (Germany) to test immunotherapy to decrease
resistance to loco-regional treatment in clinical studies (phases I and II trials) (PI C Mariette
2009 – ongoing, A Adenis 2007 under publication)
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Contracts/collaboration with GSK (USA) for basic, preclinical and clinical development of
immune therapy in oesophageal cancer to enhance host anti-tumour activity (C Mariette
2011 - ongoing)
Pleural and lung cancers
International clinical trials to test news vaccines against lung cancer (targets: MAGE-A3 (GSK)
or MUC-1(Transgene) (A Scherpereel 2009- ongoing)
International collaborations to assess the value of histone deacetylase (HDAC) inhibitors to
overcome tumour cells resistance to apoptosis, alone or in combination with chemotherapy,
in pre-clinical models and in clinical trials for malignant pleural mesothelioma or small cell lung
cancer (PI A Scherpereel): MSD trial (vorinostat – closed), ELCWP 01062 trial (valproic acid –
closed, publication Eur Respir J 2011), IRIS/Servier (S78454: 2010 - ongoing), ELCWP 01081 trial
(valproic acid: 2010 - ongoing)
International collaborations to assess the value of non reversible EGFR TKI (A Cortot – 1
publication) or anti-MET therapies to overcome tumour cells resistance to anti-EGFR TKI in non
small cell lung cancer (NSCLC): pre-clinical models (D Tulasne and A Cortot) and clinical trial
(A Scherpereel – ARQ197 from Daichi)
Primary liver cancer
International clinical trials testing multimodal therapy and targeted therapies directed against
primary liver cancer in collaboration with BAYER, NOVARTIS, ABBOTT, PFIZER and BMS.
- 3 Phase II trials: SEARCH : Sorafenib and Erlotinib, a RAndomised TRial ProtoCol for the
treatment of patients with Hepatocellular carcinoma; SPACE: A Phase II Randomized,
Double-Blind, Placebo- Controlled Study of Sorafenib or Placebo in Combination with
Transarterial Chemoembolisation (TACE) Performed with Drug-Eluting Beads and
Doxorubicin for Intermediate Stage Hepatocellular Carcinoma); LIGHT: Sorafenib and
Erlotinib, a RAndomised TRial ProtoCol for the treatment of patients with Hepatocellular
carcinoma.
- 6 phase III trials: BRISK FL (first line brivanib vs sorafenib); BRISK PS (second line brivanib vs
placebo); BRISK TA (brivanib vs placebo after TACE); STORM (Randomized, double-blind,
placebo-controlled study of Sorafenid as adjuvant treatment for hepatocellular
carcinoma after surgical resection or local ablation); SUN (first line sorafenib vs sunitinib);
EVOLVE (second line everolimus vs placebo).
- 1 phase IV trial: GIDEON (Nexavar Non - Interventional Study in HCC)
National clinical trial on the behalf of PRODIGE-FFCD group: SATURN (sunitinib vs placebo
after DC BEADS TACE)
Collaboration with a veterinary platform (ONCOVET and OCR), working with canine models of
spontaneous liver tumours (see chap III.3.2.1) in Pre-human phase 1 studies.
Head and neck
International collaboration on prevalence of HPV-associated or pharyngeal cancer (Centre
Oscar Lambret as the French representative for the International survey coordinated by
Maura Gillison, MD, John Hopkins Hospital)
International collaboration (US, EORTC, GORTEC) on larynx preservation guidelines and
clinical research (JL lefebvre, Centre Oscar Lambret)
Collaboration with Merck-Serono, Boerhinger-Ingelheim, Amgen, Genmab for clinical
evaluation of anti-EGFR in jlocally advanced or in recurrent/metastatic head and neck
cancers.
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National (INCa) contract for morphologic and molecular evaluation of head and neck
cancer in patients without known risk factors
National contract for evaluation of salivary test for early detection of head and neck cancer
Collaboration with a veterinary platform (ONCOVET and OCR), working with feline and
canine models of spontaneous head and neck tumours (see chap III.3.2.1) in Pre-human
phase 1 studies.
III.2.1.4. TEAMS, INSTITUTIONS AND INFRASTRUCTURES INVOLVED IN PROGRAM 1
Research Laboratories : Laboratory of Cell Division Signaling EA 4479 lille1, CNRS UMR8161,
Interdisciplinary research group, therapeutic EA 4481 lille2, INSERM U837 , CNRS UMR 8576, EA
4550, Lille1
Translational Research Pole : Centre de Biology pathologyBP, Genetic platform, tumor bank
Clinical Research Departments: Methodology and biostatistic unit, Clinical research unit and
Methodology and biostatictic unit of the COL and EA 2694 (health economy) and the Clinical
research unit of the CHRU.
Clinical Medical Departments COL: Head and neck cancer department, Urology and
digestive oncology department and CHRU:Medical oncology department, Department of
digestive and oncological surgery, Gastroenterology and hepathology department, General
and Digestive surgery, Pneumology and chest oncology CHRU,
Human and Social Sciences Departments: Registre des cancers de Lille et de sa région,
EQUIPPE EA 4018, EQUIPPE EA 4018, GERiiCO - EA4073 of lille3)
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III.2.2. MAIN TARGETS OF THE PROGRAM’S WORK
III.2.2.1. BASIC RESEARCH
Task 1: Identification of molecular and cell mechanisms linked to resistance to
treatments
Participants
JF Bodart, Y de Launoit, D Chevalier, P Delannoy, JF Goossens, A Lansiaux, T Lefebvre, O
Melnyk, JC Michalski, A Scherpereel, F Soncin, D Tulasne, I Van Seuningen
Targeted therapies interfere with specific targets needed for tumour growth, rather than
interfering with rapidly dividing cells like traditional chemotherapy. The tyrosine kinase receptors
(RTK) are well-known targets since they are often deregulated in cancers. The EGFR is one of
these targets, with monoclonal antibodies or ATP-mimetics used in therapeutic treatments in
lung, colon and head and neck cancers, displaying mutations or over-expression of the
receptor. These treatments increase significantly the survival of the responding patients.
However, non-responding or resistant patients, established during treatment, induce many
therapeutic failures. The resistances involve additional mutations of the EGFR receptor itself.
However, resistance also involves 1-overexpression of other RTKs (like the Met receptor), which
bypass the activation of the downstream signalling pathways and 2-alteration of RTKs activity
because of their interaction with different membrane partners. Thus, the identification of
molecular mechanisms from the membrane receptors to the integration of the signalling
involved in these resistances is an important issue to improve the therapeutic efficiency. Several
teams in Lille are investigating the involvement of RTK and their membrane partners in cancers of
epithelial origin. They will contribute to this task by developing new models (in vitro and in vivo)
adapted to the cancers studied in the ONCO LILLE consortium to better understand molecular
mechanisms associated with resistance to loco-regional treatments.
1. Identification of molecular mechanisms from membrane receptors to biological effects
Many patients with lung or colon cancer develop resistance to anti-EGFR therapies induced
notably by amplification of the MET receptor. The researchers of the “Institut de Biologie de Lille”
(IBL) conduct research on MET (the HGF/SF receptor) to understand the molecular mechanisms
leading to tumourigenesis and to characterize new anti-MET molecules interacting specifically
with its extracellular domain (Foveau et al., 2009 – Ancot et al., 2009). Recently, the team of O
Melnyk developed a new chemical method to synthesize, by native chemical ligation and bis(2sulfanylethyl)amido ligation, part of the MET ligand, i.e. the K1 domain of HGF/SF which has been
proved to be biologically active (Ollivier et al., in press). This approach developed at the IBL
opens new avenues to design active MET antagonists and will be extended here for the other
tyrosine kinase receptors studied. At the University of Lille 1, the team of Xuefen Le Bourhis also
studies signalling initiated by other RTKs, especially TrkA (receptor of NGF), and has notably
shown the implication of NGF/TrkA axis in breast cancer development using preclinical animal
models (Adriaenssens et al., 2008 - Lagadec et al., 2009 – Le Bourhis et al., 2010); functional
proteomics approaches being now developed to identify downstream signalling pathways. A
translational research program involving the IBL, the CHRU, the COL and the University of Lille 2 (A
Scherpereel, D Tulasne, V Fafeur, A Lansiaux and JF Goossens) is currently being conducted to
both identify and functionally characterize specific MET (and TRK) receptor mutations in antiEGFR-resistant tumours. This already led to the characterization of the cytotoxic/resistance
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activity of drugs (Gluszok et al., 2010) and the discovery of an original mechanism of EGFR
resistance in head and neck cancers (Rebucci et al., 2011).
Deregulation of other signalling pathways downstream from the RTK is also involved in anti-EGFRresistant tumours (Olivier et al., 2011). Recent data were obtained by the group of Tony Lefebvre
(University of Lille 1) on mammary and colorectal cancers cells (Olivier et al., in press) on the
Wnt/beta-catenin pathway regulated by post-translational modifications (such as OGlcNAcylation). On the other hand, the interplay between ganglioside and MET was also
demonstrated since P Delannoy‟s team (University of Lille 1) has recently shown that G(D3)
synthase expression is sufficient to enhance the tumorigenicity of breast cancer cells through a
ganglioside-dependent activation of MET (Cazet et al., 2010). Finally, an integrative approach to
decipher the complexity of the MAPK network (Bodart, 2010), which is triggered by RTK in cancer
is developed by the group of JF Bodart (University of Lille 1) and exhibits a specific dynamic
signature (Gao & Zhang, 2010).
We propose here to investigate the role of RTK deregulation in these three above-mentioned
preventable cancers, paying special attention to MET, TRK and Wnt/beta-catenin pathways. We
will also focus on the interplay between ganglioside and MET and we will develop an integrative
approach to decipher the complexity of the signalling network.
The aim of this part of the program is thus to characterize new biomarkers for orienting current
treatments and to anticipate future targeted therapies against RTK or downstream signalling with
the aim of decreasing tumour resistance to treatments. In parallel with these translational
approaches, the functional consequences of RTK signalling deregulation will be investigated in
cellular models to evaluate notably the consequences of mutations in cell transformation or the
influence of extracellular modifications associated with the tumour micro-environment, such as
acidification under hypoxic conditions, on cell survival and chemoresistance (J Vicogne and A
Lansiaux), as well as the recently identified role of EGFR as a virus entry cofactor in HCV-induced
hepatocarcinoma (group of N Delhem at IBL). We will exploit these established models to study
the potential role of such phenomena in the targeted cancers. In a preliminary step, we will
examine expression levels and/or the mutation status of the studied markers. Functional studies
will then be performed to exploit the knowledge gained by these teams in newly established cell
models: oral, oeso-gastric (already available in the team of I Van Seuningen) and mesothelioma
cancer cells.
2. Role of the membrane partners of RTKs in resistance to loco-regional treatments
(chemoresistance)
In close relationship with programs from §1, several laboratories in Lille have developed research
on oncogenic receptor membrane partners (mucins, gangliosides…) to evaluate their
implication in resistance of tumour cells to loco-regional treatments.
At the JPARC research Centre (University of Lille 2, the team of Isabelle Van Seuningen (Inserm
UMR837, team 5) has shown that the MUC1 and MUC4 mucins are overexpressed in various
cancers of epithelial origin, including oral and oeso-gastric cancers, participate in chemo
sensitivity of tumour cells and are direct actors in tumour progression, as they are membrane
partners of EGFR (MUC1) and ErbB2 (MUC4) (Jonckheere & Van Seuningen, 2008 - 2010). Mucins
are thus phenotypic markers of tumour differentiation (mucinous versus non mucinous),
prognostic markers (over-expression and altered localisation of membrane mucins are often
associated with tumour poor prognosis and/or with tumour drug resistance), and diagnostic
markers (MUC1 detection in numerous epithelial cancers). For many years, members of this team
(I Van Seuningen, P Pigny, G Huet, M Perrais) have developed strong translational research with
several clinical departments of the Lille CHRU (MC Copin (CBP, tissue expression), Nicole Porchet
(CBP, mutations/polymorphism/methylation), JP Triboulet/C Mariette (digestive surgery, oesogastric cancers), FR Pruvot (digestive surgery, colon and pancreatic cancers), and A Villers (renal
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cancer). Moreover, mouse and rat preclinical models of epithelial carcinogenesis have been
developed by this team or are available thanks to strong international collaborations. Finally,
spontaneous models of naturally occurring epithelial tumours (head and neck and hepatic
tumours) will be available (OCR, Oncovet) to secure the preclinical to clinical transition of
diagnostic, prognostic and more important therapeutic candidates.
Alongside the research on oeso-gastric cancers already developed in this team by Christophe
Mariette (Piessen et al., 2009), it is now proposed to initiate parallel research projects on the role
of mucins in the other cancers studied in ONCO Lille consortium (head and neck, liver).
Continuing the strong collaborations with the pathology department of the Lille CHRU (MC
Copin), we now propose to investigate, retrospectively and prospectively, expression levels of
membrane-bound mucins in tumour tissues for a correlation to loco-regional treatment
resistance. The studies proposed in this project (biomarker identification, structure-function
relationships) will benefit from the knowledge and expertise gained from the rat model of refluxinduced oesophageal cancer, developed in the team (FRM-label team). The ongoing
establishment of the same model in mice will be very useful in order to study the role of reflux in
genetically modified mouse models either obtained in collaboration or developed in the
laboratory. More recently, this team (MP Buisine) has found a correlation between mucin gene
methylation and tumour differentiation (MSI/MSS colorectal cancer). Detection of mucin gene
methylation in epithelial cancers is thus a promising (prognostic, predictive) tool for clinical
anticipation of tumour resistance, and will be tested in the cancers studied in the ONCO Lille
consortium (Van Seuningen & Vincent, 2009).
Based on the experience gained by this team that established numerous chemoresistant cellular
models (colon, pancreas, kidney) (Jonckheere et al., 2009; Aubert et al., 2009; Dessein et al.,
2010; Merlin et al., 2011), new models will be developed to study the role of RTKs membrane
partners in oeso-gastric, lung and liver cancers and their resistance to chemotherapeutic drugs.
These cellular models will be also very useful for studies developed by research teams in §1 of this
task.
3. Angiogenesis, tumour endothelium and escape from immunity
Tumour blood vessels are essential for the growth of most solid tumours and for metastasis. The
tumour blood vessel endothelium, although imperfectly tight, actively protects tumour cells from
the immune system through its barrier function. Tumour escape from immunity can be achieved
by preventing the infiltration of effector immune cells through the down-regulation of endothelial
adhesion molecules. F Soncin‟s team (IBL) has originally characterized Egfl7 (VE-statin) as
specifically expressed by blood vessel endothelial cells in normal organs during development
and in the adult and shown that Egfl7 alters blood vessel elastogenesis (Soncin et al. 2003 Lelièvre et al. 2008). This team has recently shown that Egfl7 promotes tumour growth and
metastasis by protecting tumours from the host immune response through the down-regulation
of leukocyte adhesion molecules by tumour endothelial cells (Delfortrie et al. Cancer Res, in
press). In human cancer, expression levels of egfl7 is deregulated and correlates with a higher
tumour grade in glioma and in colon cancer patients, and with a poorer prognosis and higher
metastatic score in hepatocarcinoma patients. The current projects are aimed at understanding
the role of Egfl7 and its partners in the development of tumours and at assessing the correlations
between angiogenesis, egfl7 expression, immune status and prognosis in patients having the
different cancers studied in this project. The benefit of spontaneous large animal tumour models
(which could be provided through collaboration with OCR and Oncovet) over mouse models in
this topic is evident, as the study of neo-angiogenesis is simplified by the large size of tumours,
allowing vascular tissue isolation. Through collaboration between the Biology platform and OCR,
we could validate a highly predictable preclinical model for study of anti-angiogenic drugs
toxicity and efficiency.
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Pathologies
Head and neck, oeso-gastric, primary liver, lung and mesothelioma cancer
Deliverables
(M12) Validation of the signaling pathways in targeted cancers
(M24) Validation of the identification of molecular mechanisms associated to RTK and Mucin
activity in the targeted cancers
(M 36) Develop animal models (murine xenografted...) for the study of resistance to treatment
or angiogenesis in targeted cancers.
Task 2: Animal models to determine physio-pathological processes linked to primary or
secondary tumour resistance
Participants
IMPRT (D Taillieu et T Hubert), Tumour model platform (IBL), IFR 114, Oncovet Clinical research
(D Tierny), U837 (I Van Seuningen, C Mariette)
Objectives
To identify physio-pathological processes leading to chemoresistance and peritoneal
dissemination in gastric signet ring cell carcinomas (C Mariette):
Having shown in a local and national cohort studies (Piessen Ann Surg 2009, Messager Ann Surg
2011, Mariette JCO 2012 in press) that gastric adenocarcinoma, especially signet ring cell
histology when compared to well-differentiated adenocarcinoma, are characterized by (i) a
poor prognosis, (ii) a high lymph node and peritoneal affinity and (iii) a high degree of
chemoresistance, in addition to clinical trials funded to identify an optimal therapeutic strategies
(Inca PHRC grant phase II/III trials 2011), cellular models and a dedicated mouse model have
been created to identify the physiopathologic endpoints explaining tumour characteristics and
chemoresistance
To understand the carcinogenetic sequence mechanisms from metaplasia to adenocarcinoma
in an oesophageal rat model
ubmitted to biliary and acidic reflux, in order to identify key factors leading to cancer and
sustaining chemoresistance (numerous grants from Ligue contre le Cancer,
and team
labellisation from the Fondation pour la Recherche Medicale Pi C Mariette)
To assess presence of diagnostic and therapeutic targets, and response of tumour to treatment in
canine models of spontaneous head and neck and liver tumours (Collaboration with a
veterinary platform ONCOVET and OCR).
Already used dog models represent a reliable model of naturally occurring head and neck and
liver tumours, and these share many similarities with human tumours. Similar diagnostic and
follow-up imaging procedures and treatments could be proposed in these species, and serial
biopsies of the tumour could be obtained. They share also a natural history, epidemiological and
environmental factors and response to treatments with their human counterpart. “Pre-human
phase 1 studies”, providing information on safety and efficacy of both diagnostic and
therapeutic modalities can be consequently reliably be carried out.
To propose and validate a preclinical model of oeso-gastric spontaneously resistant tumours in dogs,
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Ffactors explaining tumour characteristics and chemoresistance identified in mouse models will
be validated. Additionally, study tumour dormancy phenomenon, in interaction with program 2,
will be extensively studied in a model of canine mammary carcinoma and non-Hodgkin
lymphoma, a model in which tumour dormancy with systematic and (relatively) rapid relapse is
observed in most case within one year after initial treatment-induced remission.
Pathologies
Oeso-gastric cancers, liver and head and neck cancers.
Deliverables
(M12) identification in canine models of key factors (tumoral and host-related) leading to
tumour resistance. Dogs will be treated with previously published protocols of surgery,
radiation therapy and/or chemotherapy. Previously published and newly identified negative
prognostic factors will be used for further stratification of canine patient.
(M 12) Identifying molecular markers from available induced and spontaneous animal models
(M24) Specifically designed therapeutic strategy will be proposed in prospective clinical trials
using :
- previously identified prognostic markers for tumoral and host-related résistance ;
- previously published data regarding efficiency and toxicity of conventional radiation
therapy and chemotherapy in dogs with spontaneous tumours ;
(M 24) Identifying new molecular markers from induced and spontaneous animal models
(M 24) Identify molecular mechanisms responsible for chemoresistance
(M48) Identify molecular mechanisms responsible for chemoresistance in targeted cancers
(M 24) Drug testing on animal models
(M 36) Publication or patent: Animal models for other locations
(M 48 - 60) Develop clinical trials in humans
These studies will allow identification of tumour response to multimodal therapeutic strategy
through serial tissue sampling.
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III.2.2.2. TRANSLATIONAL RESEARCH
Task 1: Genetic, biological and pathologic factors linked to host and tumour resistance
Participants
N Porchet, Copin MC, A Scherpereel, S Dharancy, C Mariette, JL Lefebvre, D Tierny
Objectives
To identify tissue and molecular makers linked to response to loco-regional treatment and
prognosis
Based on the dedicated platforms (see paragraph VI.3), the aim is to develop and validate new
tissue and molecular markers characterized by a specific mutation or proteic expression or a
genic amplification. This will allow proposing a dedicated and innovative treatment for a
tailored therapeutic approach, taking into account both host and tumour factors linked to
resistance to loco-regional treatments. This translational research is based on a strong
collaboration between basic science researchers, pathologists, geneticians, surgical and
medical oncologists, as well as veterinary research and imaging research departments with a
common objective that is to identify mechanisms involved in tumour progression and resistance
Examples of some ongoing research programs are listed below:
Identification of emerging biomarkers that will escort the development of targeted therapies
in lung and mesothelioma carcinomas, already tested in phase I/II, III, clinical trials, such as
reversible inhibitors of EGFR and HER2, MET/ALK, MEK, mTOR, PI3K/mTOR inhibitors
Determining the role of TLR4/P2RX7 in oesophageal cancer chemo radiation resistance
(collaboration with the A+ research unit Inserm U848 Apoptosis, Cancer and Immunity L
Zitvogel Paris) and the Lille surgical department of surgery (C Mariette) (Apetoh et al. Immunol
review 2007)
Definition of signalling pathways involved in response to immune therapy by cetuximab in
oesogastric cancer (PI C Mariette, Merck-Serono sponsorized grant 2010)
Identification of mechanisms involved in the immune host stimulation through immunonutrition
administered during chemo(radiation) and surgery in oeso-gastric cancers (PI C Mariette,
Nestlé sponsorized grant 2010
Methylation pattern of the mucin genes: predictive factors of tumoral resistance
(collaboration with Inserm U837-Team 5) (Vincent A and Van Seuningen I, Expert Opin Med
Diagn 2009)
Understanding recurrence through mechanisms of metastasis (link with program 2): Having
shown that chemotherapeutic agents led to the emergence of residual chemoresistant
cancer cells that highly expressed the chemokine receptor CXCR4 and that this receptor
played a crucial role in invasion of collagen matrix and metastatic dissemination in marine
xenograft models(Dessein et al Cancer Res 2010), this model can lead to identify common
mechanisms linked to resistance to chemotherapy agents among targeted cancers.
Pathologies
Oeso-gastric cancer, lung cancer and malignant mesothelioma, head and neck cancer
Deliverables
(M12) emerging biomarkers for targeted therapies
(M12) Methylation of mucin genes as predictive markers
(M36) murine xenograft models
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Task 2: Imaging techniques for early identification of tumour resistance
Participants
I. Fournier, D. Huglo, M. Salzet, D. Tierny, E. Lartigau
Objectives
In vivo cancer imaging technology needs specific targets. It implies simultaneously tumour
localisation and following the tumour biology. This needs to increase multimodal imaging like PET
and Computer Tomography (CT) or PET/MRI. Traditional clinical measures of relapse include
disease progression, usually defined as a 20% or greater increase in tumour size, appearance of
new lesions, or death. SPI offer a large imaging platform with various imaging modalities relying
on a large number of various instrumentations offering the opportunity for high level translational
research to be applied for cancer relapse and resistance to treatments. In SPI, multimodal
imaging will also associate in vivo imaging to ex vivo molecular imaging (MSI) for a better
diagnosis by combining MRI, PET-SCAN, CT-SCAN technologies to mass spectrometry imaging
and biophotonic in order to give molecular information through new proteins or specific miRNA
detection. This allows covering from very fundamental research on resistance of host and tumour
for better understanding of biological mechanisms involved and for defining new key molecules
of these signalling pathways up to translation better diagnosis and prognosis of resistance or for
looking to new therapeutic targets and treatments. Fundamental research will start from cellular
models to be translated to animal models up to patient outcome thus allowing to improve the
uptake of patients according to inter individual variability for more personalized medicine.
1. To image known molecules in cancer resistance from basic and clinical research.
The aim of this first objective is to better understand the role of these particular molecules in the
resistance and to define the underlining mechanisms through increased knowledge on signalling
pathways. This objective is highly integrative since it will cover basic research on cellular models
up to functional imaging in medium size animals with spontaneous tumours which are closer to
human pathologies. This will be undertaken under several angles and at decreasing scale range
(mm down to nm scale) using the various imaging modalities available at the ONCO Lille SPI
Platform.
In this context, due to the fact that cell signalling pathways play a central role in cancer cell
growth, survival, invasion and metastasis and the fact that discovering the "circuit maps" of these
signalling pathways seems a high challenge for detecting novel therapeutic strategies, a large
effort will be concentrated to image both specific inhibitors of such pathways (drugs, miRNA,
cytotoxic antibodies), localize into the tumours the efficiency of such therapeutic tools and the
impact though functional and molecular imaging of these treatments on the tumour. In this
context, anti-MET molecules developed by the ONCO Lille teams will be tracked by ONCO Lille
SPI Platform using multimodal image technologies in order to get a complete integrative
response from functional to molecular images and from global to intracellular response. For this,
models animals will be firstly used and anti-MET (drugs, therapeutic antibodies will be labelled
with radioisotopes such as 64Cu) for PET-Scan analysis in conjunction with MRI images in order to
follow the inhibitor in vivo. Resected tumour will be then analyzed in whole body mass
spectrometry imaging (MSI) in order to localize and quantify the deep access of the inhibitor into
the tumour and its impact in the tumour proteome. Biophotonic imaging will give the sub cellular information about the localization of the inhibitor into cell tumour for the understanding
the mechanism of action of the inhibitor for evaluating the resistance that will occur during the
treatment. Similarly, in order to better understand the interaction between gangliosides and MET,
labelled anti-Gangliosides will be developed, used on animal models and will be trace by PETSCAN/MRI. Again, resected tumour will analyzed by MSI and the interaction between the lipid
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and the MET will be analyzed at a molecular level by giving the spatio-temporal localization of
the interaction and the partners present in the same localization. Resistance to anti-EGFR will be
also undertaken by focusing on Wnt/beta catenin pathway through targeting MAP kinase
pathway partners by labelling each of them and image them by PET/MRI.
Moreover, fundamental studies on tumour resistance have shown the role of mucins like MUC1
and MUC4 in various cancer including oral and oeso-gastric cancers. These Mucins have
proteins partners EGFR and ErB2. It is thus important to understand such interaction in course of
tumour developments and find the specific partners implicated due to their interaction. Animals
models developed at ONCO Lille or ONCOVET will be used. Specific antibody tracers for MUC1
and MUC4, PET tracers will be developed and used for in vivo immuno- PET-SCAN imaging.
Immuno-PET is a quantitative imaging procedure before or concomitant with
radioimmunotherapy. Radioimmunotherapy (RIT), consisting of radionuclides coupled to
monoclonal antibodies (mAbs) like 90Y-ibritumomab tiuxetan (Zevalin; IDEC Pharmaceuticals)
and 131I-tositumomab (Bexxar; Corixa Corp.) will be used for this project. Coupling PET-SCAN to
MSI will allow getting antibody distribution in the animals in course of the pathology
development and their penetration into the tumour. MSI will also bring the opportunity to see the
impact at the lipidome and proteome level of such treatments.
In the same way, the anti-angiogenic drugs, the EGFR and HER2, MET/ALK, MEK mTOR,
P13K/mTOR inhibitors will be followed in the whole body animal by PET/MRI and their distributions,
quantification in tumour by qMSI developed by IMABIOTECH SAS.
Considering the teams working on the Interaction between TLR4/P2X7 or CXCR4, such
fundamental work will be undertaken firstly by biophotonic imaging for understanding the
cellular and molecular mechanisms occurring during their interaction using of OxATP and brilliant
blue G antagonists of P2X7I. But also, by the development of [18F]-ML-10 as PET radiotracer, this
will give access to in vivo imaging for such receptor and its partners.
Thus it is now clear that all markers, inhibitors, drugs, antibodies developed by ONCO Lille Teams
will be directly analyzed and imaged by SPI. This is a complete close interaction between
fundamental researches to translational research through the development of specific imaging
technologies in close interaction.
2. To search for new key players of cancer resistance mechanisms in order to define new early
diagnosis and prognosis markers.
This objective can be achieved at different level using different imaging modalities. MALDI Mass
Spectrometry Imaging has demonstrated high potential for highlighting molecular contents
regulation demonstrating change of cell phenotypes up to identification of these molecules
through structural elucidation strategies for many endogenous compounds such as metabolites,
lipids, peptides and proteins. MALDI MSI group of ONCO Lille has previously demonstrated the
identification of new potential markers of ovarian cancer in prospective or retrospective studies
using archived hospital bank samples. Similar methods will be applied to find new compounds
that could be use for early diagnosis of cancer resistance. The found markers will be crossvalidated using histology and IHC through the pathology platform of C2RC.
3. To study the impact of new treatments or new drugs.
Based on fundamental knowledge from the basic and clinical research new treatments
combining several already known treatments such as known drugs with radiotherapy will be
assayed on animal models in particular medium size animal models with spontaneous tumours.
New potential therapeutic targets discovered through the collaborative work between teams
will be used for the development of new drugs such as therapeutic antibodies. Drug distribution
will be studied using the various imaging modalities. In vivo imaging will allow performing fine
kinetic studies of drugs distribution. MSI will be used to obtain drug distribution at the scale of a
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few cells in sections of organs or in whole body sections for rodent models. MSI will also bring
knowledge on the possible identification of metabolites and their localization as well as highlight
changes of the molecular content in the region targeted by the drugs. Biophotonic will be used
for subcellular localization of the drugs giving better understanding on the drug‟s action
mechanism of action. Combined PET/CT modalities is of added value here since it will allow to
define from animal models, the response to treatment in patients after e.g. chemotherapy of
radiation therapy though FDG uptake in cancerous tissues.
4. To use the acquired knowledge to define new functional imaging protocols for patients.
This objective is aimed at achieving diagnosis and prognosis of cancer resistance by in vivo
imaging screening and therefore determining the better treatment protocol to follow in order to
prevent resistance to this treatment using new treatments or drugs in a more personalized
approach. Here we particularly aim in promoting in vivo imaging for diagnosis trying to limit
biopsy uptake from patients because of the need of surgery and because of possible side
effects of regular biopsies on the development of carcinoma.
5. To develop new cutting-edge methodologies to improve the application abilities of the SPI
platform.
New methodologies using imaging modalities will help to gain new knowledge on cancer
resistance. Combined PET/MRI imaging that is to be obtained through the SMART project will be
used to improve imaging by giving access to more information. Such an instrument will help to
resolve difficulties in studying the kinetics of drug distribution or for the validation of new
therapeutics and markers which is difficult to achieve using separate imaging systems. Possible in
vivo monitoring through Mass Spectrometry is also another challenge to screen early diagnotic
markers of resistance with minimal intrusion for the patients. Development of in vivo MS screening
is the opportunity to combine diagnosis and prognosis to fast treatment using new therapies
such as PhotoDynamic Therapies to destroy cells (in particularly resistant cells) through laser
irradiation. Development of new strategies of MSI is also an opportunity to increase knowledge
with special attention paid to developing MSI imaging of miRNA. In fact, specific miRNA act as
markers of pathologies.
Pathologies
Oeso-gastric cancer, lung cancer and malignant mesothelioma, head and neck cancer
Deliverables
(M24) Integrated multimodal imaging platform
(M24) Protocol for multimodal imaging of molecules known as potential target of cancer
resistance
(M36) Compendium of early diagnosis markers of cancer resistance
(M36) Protocol for multimodal imaging of new drugs of cancer resistance
(M48) New imaging methodologies
(M60) Protocol for in vivo imaging early diagnosis of patients towards cancer resistance
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III.2.2.3. CLINICAL RESEARCH
Task 1: Identification of clinical tumour and host determinants leading to resistance to
loco-regional treatments
Participants
C Mariette, E Lartigau, JL Lefebvre, P Mathurin, A Scherpereel, M Hebbar, A Adenis, , A
Lansiaux, S Dharancy, H Porte, FR Pruvot, G Piessen, A Cortot
Based on one of the highest incidence of head and neck, oeso-gastric, primary liver, lung and
mesothelioma cancer incidence in France and worldwide, the C2RC receives a considerable
volume of patients for diagnosis and treatment, 400 oesophageal cancers, > 1000 head and
neck cancers, 450 hepatocarcinomas, 450 lung cancers and 50 malignant pleural
mesotheliomas per year. This leads to an intensive clinical research activity organized around 4
major objectives described below.
Objectives
1. To identify clinical determinants and predictive factors linked to chemo(radio)resistance:
To date complementary clinical approaches have been used to identify patient subgroups most
likely to benefit from specific treatments used in head and neck, oeso-gastric, primary liver, lung
and mesothelioma cancers. Some examples are listed below
Morphological and molecular characterization of head and neck tumours non related to
tobacco or alcoholic consumption (PI JL Lefebvre, INCa PHRC grant 2007)
Predictive factors of response to chemoradiation in oesophageal cancer (PI A Adenis,
Regional Council grant)
Stereotaxic irradiation of primary liver cancer using Cyberknife technology (PI X Mirabel, INCa
PHRC grant 2008)
Stereotaxic re-irradiation of Head and Neck cancer using Cyberknife technology (PI E
Lartigau, Industrial sponsoring 2009)
Clinical factors linked to chemoresistance in oeso-gastric cancer (PI C Mariette, Fondation
pour la Recherche Medical grant 2007)
Role of chemotherapy in patients with metastatic oesophageal carcinoma (PI A Adenis, INCa
PHRC grant 2010)
Molecular and clinical factors linked to acquired resistance to EGFR TKI in NSCLC, (PI A
Scherpereel and A Cortot, industrial sponsoring Astra-Zeneca: 2010-)
Biomarkers to predict resistance to treatments in malignant pleural mesothelioma (PI: A
Scherpereel, industrial sponsoring Fujirebio and CisBio International: 2007-)
2. To develop diagnostic strategies for early evaluation of tumour resistance in order to switch
early towards an appropriate treatment:
One of the cornerstones for an early evaluation of the resistance to loco regional treatment is
imaging based diagnosis. Many trials have been funded on our site whose primary objective is
evaluate the role of metabolic imaging for a therapeutic image-guided approach, such as:
Role of the PET in the biologic targeting for conformational or modulating intensity
radiotherapy in head and neck cancers (PI E Lartigau, INCa PHRC grant 2006)
Role of PET in predictive response to neoadjuvant chemoradiation in oesophageal cancer ( PI
C Mariette, INCa PHRC grant 2002, Ann Surg In press)
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New Imaging procedure (MDCT, PET-CT) and Biomarkers to predict the resistance to antiangiogenic drugs in lung cancer and malignant pleural mesothelioma PI: A Scherpereel and
M Rémy-Jardin, industrial sponsoring Roche: 2010-; Amgen: 2011-)
3. To develop therapeutic strategies to decrease the tumour potential for resistance:
Combination of treatments is the major way employed to fight against tumour resistance,
associating frequently chemotherapy, radiotherapy and surgery. However, the optimal
sequence of combination deserves further research in the ONCO Lille consortium targeted
cancers. Moreover since the introduction of immunotherapy treatment, such as cetuximab or
bevacizumab, the impact of these therapies is under intensive research for colon and rectal
cancers but with a lower interest for cancers targeted in this program. That is the main reason
why many researchers involved in the present program have designed ongoing national or
international trials dedicated to define optimal sequences and combinations of these
treatments in head and neck, oeso-gastric, primary liver, lung and mesothelioma carcinomas,
such as:
phase III trial testing the impact of chemoradiation in stage I and II resectable oesophageal
cancers PI C Mariette, INCa PHRC grant 2002 J Clin Oncol in press,
phase II-III trial testing the role of primary surgery vs. primary chemotherapy in resectable
signet ring cell gastric adenocarcinoma PI C Mariette, INCa PHRC grant 2011
Phase I-II trial testing the impact of an immunotherapy (cetuximab) used in combination with
chemotherapy and radiotherapy to decrease tumour resistance to standard chemoradiation
regimen. PI A Adenis, Merck Serono industrial grant 2008
Role of mini-invasive surgery in oesophageal cancer Phase III trial PI C Mariette, INCa PHRC
grant 2008
Role of surgery in patients with complete morphological response to neoadjuvant
chemoradiation in oesophageal cancer PI L Bedenne - C Mariette, INCa PHRC grant 2012
(submitted)
Phase II trials (2 academic trials, 2 supported by MSD and by IRIS/Servier) testing the value of
pro-apoptotic drugs (HDAC inhibitors) to decrease the resistance to standard chemotherapy
in malignant pleural mesothelioma or in small cell lung cancer (PI: A Scherpereel and T
Berghmans). First results published in Eur Respir J 2011.
Role of photodynamic therapy combined with pleurectomy/decortication and
chemotherapy in the multimodal treatment of malignant pleural mesothelioma. PI: A
Scherpereel, INCa PHRC grant 2012 (submitted)
Kinetic assessment of tumour resistance in EGFR-mutated patients with NSCLC treated by
EGFR TKI. PI: A Cortot, INCa PHRC grant 2012 (submitted)
4. To develop therapeutic strategies to decrease the host potential resistance.
Based on the hypothesis that the host and the immune modulation may have a strong impact
on response to loco-regional treatment, various clinical approaches have been used on site,
such as:
Stimulation of the immune system through immunonutrition. Important results have been
obtained in the peri-operative setting in numerous randomized trials. The unique and original
approach developed in oeso-gastric cancer is to reinforce the host immune system during
the whole therapeutic sequence from the beginning of chemotherapy to the postoperative
care. An international trial to confirm this hypothesis is ongoing (PI C Mariette, Industrial
European Nestle grant 2011).
Targeting tumour cells via patients‟ immune system stimulation. Via a Lille partnership with the
US GSK pharma, a specific target will be tested in oesophageal cancers (MAGE A3) to
develop a dedicated vaccine therapy through preclinical, phases I, II and III trials (PI C
Mariette, GSK grant 2011) – also a phase II trial in resected NSCLC (PI: A Scherpereel)
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Evaluating the optimal delay for hepatic transplantation after acute host assault: results from
a national survey (Mathurin P, Dharancy S et al, New Engl J Med 2011).
Pathologies
Head and neck, oesophageal, gastric, primary liver, lung carcinomas and malignant pleural
mesothelioma
Deliverables
M6-M24 : Identification of clinical predictors for resistance from existing data-bases and
numerous ongoing trials
M6-M24: Identification of biological and cellular predictors for resistance
M6-M48: Animal modelisation for resistance
M36-M48: Design clinical trials testing therapeutic strategies based on host/tumour predictors
for resistance identified
M6-M60: Integration of data coming from research to the bed side
M0-M60: Diffusion of the knowledge through publications, national and international
communications and local networks
Task 2: To tailor clinical trials with the aim to identify factors linked to resistance
Participants
Clinical research Unit of the COL and Clinical Investigation Centre-Inserm (P Devos, A Kramar,
A Duhamel, S Clisant, N Penel)
Objectives
1. To design clinical trials dedicated to subgroups of patients, characterized by the host and
tumour resistance factors previously identified
Clinical breakthroughs will be possible if we conduct clinical trials focusing on particular
populations of patients. Both host specificities (such as co-morbidities, nutritional, immune
status…) and tumour specificities identified through retrospective cohorts, translational and basic
research results, will be integrated in the inclusion criteria of these trials. The targeted populations
in the present Program do not usually meet the eligibility criteria in clinical trials launched by
industrials, so it is necessary to design pragmatic trials adapted to medical constraints. This
implies also that the Onco Lille Consortium includes a robust multidisciplinary team of
methodologists, biostatisticians, regulatory affair specialists able to launch multicenter clinical
trials.
2. To design clinical trials based on the evaluation of combined strategies
Whereas combined strategies are frequently used, concomitantly or sequentially in practice, the
vast majority of clinical trials are dedicated to one step of the cancer patient route, leading to
some difficulties to integrate results obtained into the overall therapeutic sequence. Current
therapeutic strategies result consequently more in a juxtaposition of proven concepts than in a
well- balanced integration of these concepts during the longitudinal phase of cancer treatment.
As examples, (i) clinical trials investigating the role of surgery and combined treatment including
surgery require a specific expertise (oncologic surgeon with expertise in clinical research and
medical oncology endpoints), (ii) clinical trials integrating survival endpoints combined with
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human sciences endpoints may lead to integrated patients‟ opinion in the treatment choice, (iii)
ancillary translational research programs should be specifically designed to evaluate factors
linked to resistance. Such trials are much more complex to conduct than classical trials
investigating systemic treatment and deserve a strong expertise and important collaborations.
Moreover, they are less frequently funded by industrial sponsors and thus need the help of
academic groups, justifying the importance for the ONCO Lille consortium to be labelled.
3. Methodology for the identification, validation and use of factors linked to tumour resistance
The objective is to identify clinical, biological socio-economic and environmental factors
associated with tumour resistance. We will use statistical methods adapted to the search for
prognostic factors for loco-regional control by taking into account competing oncological
events such as death, metastases and second primaries. In particular, the multivariate Cox
model will be used to evaluate the impact of these factors, especially loco-regional control) on
cause specific hazards. The Fine & Gray multivariate model will be used to evaluate their impact
on cumulative incidence functions. These two approaches are necessary since the factors
studied may behave differently on each component of progression-free or disease-free survival,
often leading to contradictory results.
We will also use innovative methods for the analysis of complex incomplete data (severity of
toxicities, recurrent events during follow-up) in order to construct prognostic scores (MBU
platform). Members of the EA2694 team have renowned methodological experience in the
domain of data analysis in the presence of missing data, competing risks, and recurrent events.
In order to identify factors of resistance, we will use the constituted cohorts within the scope of
this project.
The factors identified will then be validated with either re-sampling techniques or with data from
external cohorts.
Once validated, these factors could be taken into account in the selection and/or stratification
of patients in phase I/II clinical trials (MBU platform), in order to optimizer the design of phase III
clinical trials: stratification, matching or adjustment.
Pathologies
Head and neck, oesophageal, gastric, primary liver, lung carcinomas and malignant pleural
mesothelioma
Deliverables
M12-M30: Identification of prognostic scores
M30-M36: Validation and publication of results
M36: Integration of prognostic scores, into the design of clinical trials
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Task 3: Partnerships intensification, for accelerated integration of data coming from
clinical, image-based, biological and pathological research programs to the bed side.
Participants
ONCO Lille consortium management and scientific committee. The purpose of this task is to
coordinate the knowledge and the diffusion of obtained results in ONCO Lille programs and
platforms in order to serve the global oncological community.
Objectives
to speed up and reinforce the interaction between clinical, translational and basic
researches to enhance patient survival through an accelerated and innovative tailored
therapeutic approach
to intensify research partnerships with industrial sponsors on cancers usually poorly studied: the
aim is that ONCO Lille consortium gains in visibility on such cancers
to redirect some existing models of treatment resistance in order to accelerate (i)
comprehension of the mechanisms involved in the targeted cancers and (ii) their translation
into clinical applications
to plan through the transversal and multidisciplinary scientific committee new collaborations
and innovative approaches to reinforce research efficiency and production
Pathologies
Head and neck, oesophageal, gastric, primary liver, lung carcinomas and malignant pleural
mesothelioma
Deliverables
M6-M36 : Identification of valuable results to be diffused
M24-M60: Design clinical trials and fundamental research projects to enhance results in
ONCO Lille
M0-M60: Diffusion of the knowledge through publications, national and international
communications and local networks
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III.2.2.4. CONTRIBUTION OF HUMAN AND SOCIAL SCIENCES
Task 1. Identify and model new factors of cancer over incidence and delay in diagnosis
Participants
V Christophe, JL Lefebvre, K Ligier, D Chevalier, A Berrier, P Meyer, P Camuzet, J Ton Van, B El
Rassi, G Launoy, O Dejardin, T Leroy, M Seillier, J Foncel, S Dabo, O Torres, A Lamy, G
Blanchard
Reducing the excess-incidence of cancer appears to be essential for the patients‟ vital
prognosis and their quality of life. Various factors such as socio-demographical, socioeconomical, socio-educational, socio-cultural, and socio-professional factors already explain
either this excess-incidence or late diagnosis for several types of cancers. However, these factors
do not seem sufficient to fully explain or characterize patient delay or excess morbidity in, for
example, UADT cancers. Some recent data, as well as classical theoretical models of health
behaviour emergence, suggest that some socio-cognitive and emotional determinants may
explain patient delay from a complementary point of view. Then, if one aims to modify patients‟
health behaviours to improve their vital prognosis, their quality of life, and to reduce social
inequalities regarding health, it seems essential to reckon with patients‟ representations about
health, as well as the contextual, emotional, and social determinants of their decisions and
behaviours.
Objectives
1. To identify new factors of risk of upper aero digestive tract cancers.
There is an emergency to understand factors that lead to the very high regional incidence for
the cancers targeted in this program. The current data on the known risk factors do not fully
explain all the individual and collective determinants responsible for this excess-incidence of
preventable cancers in the Nord – Pas de Calais region. Identifying new relevant factors of
preventable cancers (socio-economical, psychological, behavioural, environmental and
informational) and building interventional preventive researches related to this new dataset is a
challenge for decreasing the excess-incidence and excess-mortality in this region of France.
Knowledge of these factors will provide hope for better outcomes in the management of these
lethal conditions. An econometric model of excess cancer incidence in the Region will be taken
from the data collected at the patient level from the preceding program. This dataset will be
supplemented by a survey conducted on cancer-free individuals. This econometric approach
has the advantage of handling and testing together many factors that can potentially influence
cancer incidence. Regarding methodology, multivariate and spatial statistical techniques that
have been already applied to other fields of research will be used. This tool for primary
prevention will thus complement the analysis of late diagnosis described above. In a second
step, a multilevel and multidimensional model will be built to explain excess-mortality for these
two criteria , i.e. excess-incidence and late diagnosis.
Identifying New Risk Factors of upper aero digestive tract cancers, J Foncel, CPER Cancer
Grant, 2011.
Team publications
- Dabo-Niang, S et al. Mathematical Methods of Statistics 2007;4:1-20.
- Dabo-Niang, S, et al. Stochastic Environmental Research and Risk Assessment, 2010; 4: 487-497.
- Jouneau-Sion F et al. Journal of Econometrics. 2006; 133
2. To identify factors influencing treatment delays in targeted cancers and to reduce the
inequalities to access to care.
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On the basis of classical health psychology models, the main objective of this study is to assess if
the consultation delay of a doctor after the first UADT cancer symptoms have occurred is linked
to socio-cognitive and emotional factors, in complement of the previously cited factors. We
propose to conduct a retrospective observational multicentre study, which does not imply any
change of patients‟ medical care. Each patient with untreated UADT cancers may be included
in this study, in six (public and private) health centres which take care of about 90% of UADT
cancer patients of the North of France region. We expect to include 600 patients. The main
evaluation criterion is the length of time between the occurrence of the first symptoms of the
disease, and the first doctor consultation when these symptoms have been evoked by the
patient. This patient delay is estimated 3 ways so as to optimize data validity. Medical, sociodemographical, socio-economical, socio-educational, socio-professional, geographical, sociocognitive, and emotional factors will also be assessed by means of (1) a case report form, (2) a
questionnaire completed by the investigator in company with the patient, (3) a questionnaire
completed by the patient himself, and (4) a taped semi-directive interview of the patient by a
psychologist (for 80 patients only).
Determinants of patients‟ delay in doctor consultation in upper aerodigestive tract cancers, V
Christophe & JL Lefebvre CPER Cancer Grant, 2011.
Team publications
- Lefebvre JL, et al. J Natl Cancer Inst. 2009;101:142-52.
- Rozniatowski O et al. Head Neck 2005
- Lefebvre JL et al. Int J RadiatOncolBiol Phys. 2009;73:1293-303.
Pathologies
Head and neck and oeso-gastric cancers
Deliverables
M36-48: Development of innovative tools and dataset analysis to explain individual and
collective factors of preventable cancer over incidence (publications)
M36-60: To better identify the factors influencing the delays in the three preventable cancers
and to reduce the inequalities of access to care in order to have a direct impact on survival
(measure 19 and 21 of French Cancer Plan II 2009-2013,
M60: Define personalized accompanying action for (i) facilitating access to useful information
for decision-making in health, (ii) facilitating access to care, (iii) offering support promoting
preventive consultations of risk,
M0-M60: knowledge‟s dissemination through publications, national and international
communications and local networks.
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Task 2. Evaluation of the psychological, emotional and familial impact of clinical
research in Oncology.
Participants
V Christophe, C Mariette, N Penel,A Desauw, C Duprez, E Fournier, P Antoine, E Constant, T
Leroy, M Seillier, S Clisant, J Foncel S Dabo, O Torres, A Lamy, G Blanchard, T Leroy, L
Vanlemmens, JL Nandrino, P Antoine
The difficulties when nursing a person with cancer have been subject to numerous researches,
especially the diagnostic wandering, the impact of the disease and treatment on well-being,
quality of life, emotional, psychological and family as well as socio-professional and financial
sphere. The situation of the people with cancer as well as the difficulties encountered by their
caregivers need to be more thoroughly investigated in order to promote interventional programs
to suit the specific needs of both. The study of emotion regulation in caregivers „and patient‟s
dynamic adjustment is fundamental to understand the disease evolution, cognitive and
behaviour disorders. However, many stress management program are based on a relatively
static stress-coping model, which has been used widely in studies of family caregivers. Under this
cognitive theory, stress is conceptualized as a relationship between individuals and their
environments, which they assess cognitively as exceeding or taxing their personal and social
resources. Now, understanding the nature of the temporal dynamics of burden and care, and
the emotional processes that underpin them, as well as individual differences in the patterns and
regularities characterizing caregivers‟ and patient‟s adjustment remains one of the most
important challenges in the study of care giving.
Objectives
1. Psychological and emotional impact of the patient’s in clinical trials.
The participation of patients in clinical studies in oncology occurs in most cases following the
announcement of a bad news about their health (announcement of the diagnosis of cancer or
a disease progression). The question then arises as a consequence of such an involvement in a
context that could have undermined the psychological and emotional state of patients. Indeed,
the participation in a clinical trial could generate in patients more positive effects (related to
increased follow-up and the hope of improvement in their state of health through innovative
treatments) than negative emotional effects, such as anxiety or depression (in conjunction with
the uncertainty of the outcome of the situation, especially and even more if it is a randomized
study). Despite the ambivalence of the possible consequences, few data are currently available
on how patients live with their participation in a clinical study. The main objective is to compare
the psychological and emotional consequences of such a treatment over time (chemotherapy
or targeted therapy: effect on the type of treatment checked after the event) issued as part of
a phase II or III clinical study (cases) to those of a standard delivered apart from the study
(witnesses): quality of life, anxious and depressive symptoms, emotional and regulation
strategies.
Psychological and emotional impact of the patient‟s participation in clinical trials , V
Christophe & S Clisant INCa Grant (2009)
Team publications
- Christophe, V. et al . Psychology & Health 2008;23: 84-85.
- Leroy, T. et al. New Drugs, in press, [http://www.ncbi.nlm.nih.gov/pubmed/19760365].
- Leroy, T., et al Contemporary Clinical Trials, in press [DOI 10.1016/j.cct.2010.09.003].
- Leroy, T et al Journal of Clinical Oncology 2009; 27, e17500.
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2. Emotional and cognitive impacts of surgery and peri-operative chemotherapies in the patient
with operable gastric cancer and his/her partner.
Few published data is currently available about the emotional or cognitive impact of treatment
(surgery – chemotherapy) of a gastrointestinal cancer and in principle in operable gastric
cancer. This innovative ancillary study, which is also a pilot and exploratory study, aims to gather
a body of data in order to gain a better knowledge of the repercussions of this cancer and the
specific methods of treatment not only on the patient, but also on his or her partner, the main
natural carer. It also aims to obtain a better knowledge of how these repercussions develop in
time by means of a longitudinal approach within a context in which the vital prognosis and
toxicity of associated treatments are particularly severe.
This study takes a dynamic and systemic approach to patient treatment taking into account the
role of the family environment, and more specifically the husband/wife partnership. From this
point of view, the observation of the dyadic adjustment of the experience of the patient and
his/her partner in the course of the treatment seems extremely promising with regard to
understanding the dynamics of the relational and emotional mechanisms at stake in a crisis
situation such as discovering and treating ADCI. This is a matter of having a better grasp of the
repercussions, benefits and costs of the different treatment schedules on the overall quality of life
of the patients and their close carer, but also to stress the critical phases of this treatment by a
longitudinal approach. The main aim of this exploratory ancillary study is to compare the
development in time of the quality of life and the emotional and cognitive state of the patient,
and his or her partner, depending on the treatment arm to which he or she was allocated. This
study also aims to determine to what extent the understanding of the clinical trial, the
perception of the disease, and the coping strategies mediate or moderate the effects of the
treatment on quality of life and emotional state of the patient and his or her partner, and to
measure over time the dyadic adjustment of the quality of life, emotional state, perception of
the disease, and the coping strategies implemented by the patient-partner pair.
phase II-III trial testing the role of primary surgery vs. primary chemotherapy in resectable
signet ring cell gastric adenocarcinoma PI C Mariette, INCa PHRC grant 2011
Team‟s publications
- Christophe, V., et al. Psychological Reports 2008 ; 103, 11-22.
- Antoine, P et al. Journal of Health Psychology 2009; 14(8), 1156-1162.
- Messager et al. Ann Surg. 2011;254:684-693.
Piessen et al. Ann Surg. 2009;250:878-87.
3. To develop tools for assessing the quality of life of the patient and partner and evolution in time.
Based on the experience developed in breast cancer, this modelisation will be applied to
cancers targeted in the Program 1. A study of the quality of life of couples in which one person
has cancer at a relatively young age seems to be innovative firstly because age has a non
insignificant impact for patients (e.g. the desire to have children, educating very young children,
sex life, professional future etc.) and secondly because there is very little empirical data
available that addresses the role and the importance of close relatives and, more specifically,
partners. Yet these close relatives who naturally take the role of caregiver on a day-to-day basis
can find this very demanding. Gaining more in-depth knowledge about the experience of the
partner is undeniably an advantage in terms of improving our understanding of the experience
of the patient herself. This should no longer be a one-dimensional approach, but a dynamic and
systematic approach to managing patients within their social and family environments. To our
knowledge, there is no tool validated in French for assessing quality of life specific to this
population that can really identify the preoccupations, difficulties and needs of these women
and their partners during and after their treatment.
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The main objective was to create a questionnaire (with a patients‟ version and a partners‟
version) based on accounts of the experiences of young female patients with non-metastatic
breast cancer and their partners. In order to guarantee a temporal perspective on the impact of
the cancer from the time of diagnosis until the follow-up period after treatment has ended, four
separate groups of 100 couples (that is, 400 patients and 400 partners) will be formed according
to the patient's treatment route: 1) during chemotherapy plus or minus Trastuzumab; 2) during
treatment with Trastuzumab plus or minus hormonal therapy; 3) during hormonal therapy only;
and 4) during follow-up (after all treatment has ended). In order to test the psychometric
properties (temporal reliability and concurrent validity) of the questionnaires for the patients and
their partners, the participants will be randomly assigned to four sub-groups and invited to
respond to: 1) the questionnaire to be validated (KALI), 2) KALI plus a quality of life questionnaire,
3) KALI plus anxiety and depression scales or 4) KALI once, and then a second time two weeks
later.
Subjective quality of life scale for young women with breast cancer and their partners, V
Christophe & L Vanlemmens,
INCa, Ligue Nationale contre le Cancer, Laboratoires
pharmaceutiques Sanofi, Roche et Novartis Grant (2007-2009)
Psychometric validation of a subjective quality of life scale for young women with breast
cancer and their partners, V Christophe & L Vanlemmens , Ligue Nationale contre le Cancer ;
Conseil Régional Nord Pas de Calais, Laboratoires pharmaceutiques Sanofi, Roche et Novartis
Grant (2009-2012)
Team publication: Vanlemmens, L. et al The Breast Journal, 2011in press.
Pathologies
Head and neck and oeso-gastric cancers
Deliverables
M6-M24: Compare the quality of life and survival of patients, their understanding of the
implications of participating in a clinical research protocol, as well as their strategies and
possible difficulties in emotional regulation during the clinical trial (publications).
M12-M36: Identification and validation of therapeutic strategies to enhance or restore the
quality of life of patients and partners (publications)
M36-48: Development of innovative tools and dataset analysis to explain individual and
collective factors of preventable cancer quality of life (publications)
M60: Define personalized accompanying action for (i) facilitating access to useful information
for decision-making in health, (ii) facilitating access to care, (iii) offering support promoting
consultations therapeutic education of patients and their families to cope with the difficulties
encountered.
M0-M60: Diffusion of the knowledge through publications, national and international
communications and local networks.
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III.2.3. EXPECTED RESULTS
III.2.3.1. IN TERMS OF PRODUCTION
This program will enable a qualitative and quantitative leap for the organization of research on
the role of the tumour and host determinants in resistance to loco regional treatments, on the
production of knowledge, and a transfer to clinical applications within clinical trials. The
integrated axes of the Program will offer the possibility to reinforce the interaction between
clinical, translational and basic researches with a common goal of enhancing patient‟s survival,
quality of life and quality of care. The emerging projects and innovative results achieved will be
communicated upon within the network of clinicians and researchers of ONCO Lille using the
dissemination mechanism scheduled to be developed in the ONCO Lille program.
Building on existing research groups, platforms, and clinicians of ONCO Lille, this program will:
Enable the rapid in vivo validation in Head and neck, oeso-gastric, primary liver and pleurapulmonary cancer patients the hypotheses and concepts generated in preclinical and in
vitro tumour models. Conversely, it will enable the basic research teams to develop research
programs aiming to understand the molecular mechanisms involved in the resistance to locoregional treatments
Enable the identification of therapeutic targets and development of therapeutic strategies
and their validation in pre-clinical models and cohort studies
- Identify molecular alteration/pathways that governs tumour and host resistance
- Identify and validate targets to restore host anti-tumour immunity
- Identify and validate targets to fight against tumour factors linked to resistance
- Develop strategies to enhance therapeutic efficacy, such as anti-tumour targets
- Define new therapeutic interventions and/or therapeutic sequences to improve tumour
loco-regional controlled and patient‟s survival
Enable the development of clinical trials aiming at defining optimal therapeutic sequence
per cancer according to tumour and host factors identified
- Perform innovative trials, based on basic and translational research programs, to stimulate
long lasting host anti-tumour immune response
- Perform innovative trials, based on basic and translational research programs, to control
and go around tumour parameters linked to resistance
Enable the reinforcment and acceleration, in parallel, of empirical identification of potential
markers linked to tumour resistance based on a large amount of clinical and biological
variables registered in established data base enrolling thousands of patients with head and
neck, oeso-gastric, primary liver and pleura-pulmonary cancers.
Overall this program will have a major impact on:
The field of experimental medicine through publications in high ranking journals
The emergence and validation of novel concepts in human clinic leading to intellectual
property protection
The identification and validation of strategies, targets and drugs to reinforce host immunity
and inhibit or turn around tumour factors linked to resistance
Patients‟ care providing innovative therapeutic solutions, allowing to cure increase number of
patients exposed to such disastrous disease
Medical costs by a tailored therapeutic approach rather than global treatments for all
patients
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Increasing recruitment in clinical trials to enhance research potential and quality of care
Attraction of highly qualified scientists and MD within the SIRIC environment
Attraction of students and postdoc abroad thanks to the scientific/clinical interface provided
by SIRIC
Attraction to donators and investors
Attraction of biotechs and pharma to implant and develop within ONCO Lille their clinical
trials
III.2.3.2. IN TERMS OF DISSEMINATION OF KNOWLEDGE AND OF PROVISIONAL CALENDAR
Presentation at scientific congresses: 1 or 2 for each project line after 1 year
Scientific publications: from year 3, more than 5 publications per year in journals with IF>15
Brevets: from year 3, more than one novel patent per year protecting concepts, strategies or
drugs
Increased recruitment in clinical trials from 15% in 2011 to 25% in 2015
Presentation of the results in CME programs already in place
Training within the program plan of the SIRIC Lille-Nord de France, within and beyond the
network
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III.2.4. FOCUS ON THE EMERGING RESEARCH ASPECTS THAT MAY BENEFIT FROM FUNDING OF THE
SIRIC
To improve efficiency in loco-regional radiotherapy treatment, with the development of a
transversal Monte-Carlo dose engine.
Nick Reynaert, Thomas Lacornerie & Fabrizio Cleri – Department of Radiotherapy Centre Oscar
Lambret & Institute of Electronic, Microelectronic and Nanotechnology (IEMN))
Over the last decade, technical possibilities in external beam radiotherapy have developed
substantially (IMRT, Tomotherapy, robotic therapy, hadron therapy, image guided therapy, 4D
radiotherapy…). In addition, important improvements have been made in treatment planning
software, including options for inverse planning, and advanced dose calculation algorithms. A
Monte Carlo dose engine is currently the only algorithm having the potential to meet this
requirement, regardless of beam geometry and patient composition. The aim of present work is
to introduce a QA system based on a standardized Monte Carlo dose engine able to calculate
full 3D dose distributions for individual patients, using a DICOM interface (CT, tumour delineations,
planned gantry angles, fields/segments, MU, etc). This Monte Carlo dose engine will be able to
recalculate treatment plans for CyberKnife, Tomotherapy, IMRT and proton treatments. It will be
extended to other dosimetric systems (laser therapy, hyperthermia...)
For this purpose the MCDE system will be reprogrammed. MCDE is a full blown Monte Carlo tool
based on the BEAMnrc/DOSXYZnrc user codes of the EGSnrc system, and has already been used
intensively for benchmarking IMRT treatment planning for conventional Linacs, leading to over 20
scientific papers. No approximations are introduced and calculation time is kept within
reasonable limits, by parallelizing the calculations on a cluster.
Modelisation of morbi-mortality of primary liver cancer in France across stage of severity:
evaluation of different strategies according to amount of screening and therapeutic resources (S
Dharancy, P Mathurin):
The objective of this project is to predict the impact of early screening and treatment on
expected morbidity and mortality of patients by stage of gravity of the primary liver cancer and
in the light of current practices. The project comprises three phases. The 1st phase requires the
development of a Markov type compartmental model supplied by data obtained in studies
published on the progression of primary liver cancer and the impact of available treatments,
and mortality data by primary liver cancer from CepiDc. Assumptions on patients‟ distribution by
stages will be based on data obtained from: (i) the Finistere registry (data published in
Gastroenterologie Clinique et Biologique); (ii) an ongoing study from the register of Calvados
(data supplied by the Dr. Isabelle Ollivier-Hourmand, CHRU Caen) and (iii) databases from the
services of hepato-gastroenterology from consortium CIRRAL on primary liver cancer. This model
will allow simulating the outcome of patients according to their degree of severity. The 2nd
phase will consist in the validation of the model predictions over 1 year using epidemiological
data from French Cancers registries collected by the FRANCIM network. This 2nd phase will be
performed with a close collaboration with Mr Guy Launoy, director of the Calvados Cancer
Registry. This phase will allow validating the robustness of the model. Once the model is
validated, the 3rd phase will test the impact of different scenarios for screening and treatment
on the morbidity and mortality of HCC. Our hypothesis is that early detection of HCC could
increase patient access to curative treatment and hence their survival. Such information will help
to define public health goals in the management of primary liver cancer.
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III.2.5. APPENDICES
III.2.5.1. INTEGRATION WITHIN THE WHOLE SCIENTIFIC PROJECT – ARTICULATION WITH THE
OTHER PROGRAMS
The Program 1 will achieve significant breakthroughs in the modelling of host and tumour
resistance to initial loco-regional treatments. Even if initial resistance of cancer cells to treatment
can explain early relapse, late relapse can only be explained by the persistence of a small
population of cancer cells that remains dormant for a long period of time, defining tumour
dormancy that is studied in Program 2. These 2 strongly linked programs will integrate biological
and clinical research platforms, imaging and humans sciences developments, particularly in the
field of comprehensive handling of the disease for the patient and the family (global care):
since the same platforms are involved in the Programs 1 and 2, that will naturally reinforce links
between the two programs. Morover, dissemination of knowledge will be directed towards
patients, general and specialist practitioners, political authorities, healthcare providers and
teaching activity on the same basis for the two Programs. Bringing together new data on the
mechanisms of resistance and persistence to treatment in human tumours, biological models,
imaging and clinical research will help to drive new studies in the field of adaptive and
personalised medicine within a similar and interconnected approach
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III.2.5.2. PLANNING
2012
MONTHS
1
2
3
4
5
6
7
2013
8
2014
2015
2016
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Scientific program 1: tumour and host resistance to loco-regional treatments
Basic Research
Task 1 : Identification of
molecular and cell
mechanisms linked to
resistance to treatments
Task 2 : Animal models to
determine physio-pathological
processes linked to primary or
secondary tumour resistance
Signaling pathways in
targeted cancers
validated
Identification of molecular
mechanisms associated to RTK
and Mucin activity in targeted
cancers validated
Key factors (tumoral et hostrelated) leading to tumour
resistance identified in canine
models
Specifically designed therapeutic
strategy proposed in prospective
clinical trials
Molecular markers
identified from available
induced and spontaneous
animal models
Animal models developped for
the study of resistance to
treatment or angiogenesis in
targeted cancers
Molecular mechanisms
responsible for
chemoresistance identified in
targeted cancers
New molecular markers identified from
available induced and spontaneous
animal models
Molecular mechanisms responsible for
chemoresistance identified
Drug testing on animal models
Start of clinical
trials in humans
Animal models
for other locations
End of clinical
trials in humans
Translational Research
Emerging biomarkers for targeted therapies
Task 1 : Genetic, biological
and pathologic factors linked
to host and tumour resistance
Murine xenograft models
Methylation of mucin genes as predictive markers
Task 2 : Imaging techniques
for early identification of
tumour resistance
Protocol for multimodal imaging of
molecules known as potential
target of cancer resistance
Integrated multimodal
imaging platform
Compendium of early diagnosis
markers of cancer resistance
Protocol for multimodal imaging of
new drugs of cancer resistance
New imaging
methodologi
es
Protocol for in vivo
imaging early
diagnosis of
patients towards
cancer resistance
Clinical Research
Start of identification of clinical predictors for resistance
from existing data-bases and numerous ongoing trials
Start of animal modelisation
for resistance
Task 1 : Identification of
clinical tumour and host
determinants leading to
resistance to loco-regional
treatments
End of identification of clinical predictors
for resistance from existing data-bases and
numerous ongoing trials
End of identification of biological
and cellular predictions for
resistance
Start of identification of biological and
cellular predictions for resistance
End of animal
modelisation for
resistance
End of design clinical trials
testing therapeutic strategies
based on host/tumour
predictors for resistance
Start of design clinical trials
testing therapeutic strategies
based on host/tumour predictors
for resistance identified
End of integration of data
coming fom research to the bed
side
Start of integration of data coming fom
research to the bed side
Start
of diffusion
of the
knowledge
trough
Beginning
of idiffusion
of the
knowledge
troughpublications,
publications, national and
national and international
communications
local networks
international
communications
and localand
networks
End of diffusion of the knowledge trough publications, national and
international communications and local networks
Prognostic scores
Start of
identified
identification
of prognostic scores Start of validation and publication
results
Task 2 : To tailor clinical trials
with the aim to identify factors
linked to resistance
Prognostic scores integrated into the design of clinical
Results validated and publicated
Start of identification of valuable
results to be diffused
Task 3 : Parterships
intensification for accelerated
integration of data coming
from clinical, image-based,
biological and pathological
research programs to bed side
End of identification of valuable
results to be diffused
End of design clinical trials and
fundamental research projects to nehance
results in ONCOLille
Start of design clinical trials and
fundamental research projects to enhance
results in ONCOLille
Start of diffusion of the knowledge trough publications, national
and international communications and local networks
End of diffusion of the knowledge trough publications, national
and international communications and local networks
Human and social sciences
Initiative tools and dataset analysis
developed
Start of development of initiative tools and dataset
analysis to explain individual and collective factors of
Task 1 : Identify and model
new factors of cancer over
incidence and delay in
diagnosis
Personalized accompanying actions defined
Start of knowledge'dissemination trough publications, national and
international communications and local networks
Task 2 : Evaluation of the
psychological, emotional and
familial impact of clinical
research in oncology
Start of publications :
quality of life and
survival of patients,
understanding of of
clinical research
protocol, emotional
regulation during trials
End of publications : quality of life
and survival of patients,
understanding of of clinical research
protocol, emotional regulation during
trials
End of knowledge'dissemination trough publications, national
and international communications and local networks
Start of development of initiative
tools and dataset analysis to
explain individual and collective
factors of preventable cancer over
quality of life
1
2
3
4
5
6
7
2012
123
8
Initiative tools and dataset analysis
developed
Personalized accompanying
action defined
End of publications : therapeutic strategies
to enhance o restore the quality of life of
Start of publications : therapeutic strategies to enhance
o restore the quality of life of patients and partners
Start of knowledge'dissemination trough publications, national and
international communications and local networks
MONTHS
Factors influencing the delays in the three preventable
cancers better identified
Start of identification of the factors influencing the delays
in the three preventable cancers
End of knowledge'dissemination trough publications, national and
international communications and local networks
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
2013
SIRIC - CALL FOR APPLICATIONS 2012
2014
2015
2016
APPLICATION FILE
III.2.5.3. BUDGET
K€ HT
2012
2013
2014
2015
2016
TOTAL
EXPENDITURES
Program 1 : Resistance
475
375
400
475
375
2 100
Staff for the current scientific projects
Equipment
Running
Support for the emergence of new scientific projects
275
100
25
75
275
275
275
25
75
50
75
275
100
25
75
1 375
200
150
375
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25
75
APPLICATION FILE
III.3. Tumour dormancy and persistence
Program coordinator: Pr. Bruno Quesnel, MD, PhD, Inserm research team U837-E3 “Factors of
persistence of leukemic cells”, Clinical Department of Haematology, CHRU Lille
[email protected] and [email protected]
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III.3.1. MAJOR THEME OF THE PROGRAM
III.3.1.1. SCIENTIFIC OBJECTIVES OF THE PROGRAM
Many cancers respond to initial treatment, but most relapse, sometimes after decades. For
instance, the recurrence of breast or prostate cancer frequently occurs through late metastasis
after successful surgical removal of the primary tumour. In some tumour types, the entire cancer
cell population has been exposed to an efficient systemic therapy. Acute leukaemia, for
example, enters a complete remission phase after intensive chemotherapy. Nevertheless,
relapses occur from a population of residual cells. Thus, recurrence in cancer is the rule rather
than the exception, and targeting mechanisms that allow long-term persistence of residual
cancer cells after treatment would likely improve survival.
The biological factors that allow recurrence remain poorly understood. Initial resistance of
cancer cells to treatment can explain early relapse (cf program1). However, late relapse can
only be explained by the persistence of a small population of residual cells that remain dormant
for a long period of time. This phenomenon of long-term persistence of cancer cells that do not
grow is called tumour dormancy[1]. During this period, residual cancer cells remain in equilibrium
with the host. [2]. Mechanisms that maintain this long-term equilibrium between residual tumour
cells and host tissue or disrupt this equilibrium in favour of the tumour cells, leading to clinical
relapse, have remained poorly understood. Few experimental models of tumour dormancy are
available, and dormant tumour cells in humans are difficult to isolate, making scientific progress
relatively slow. However, several experimental models have led to the discovery of mechanisms
of dormancy. Reduced angiogenesis results in tumour dormancy in NOD-SCID models. The lack
of an interaction between the microenvironment and the residual tumour cells can also lead to
dormancy. Recent results have also demonstrated in new animal models that a balance exists
between host anti-tumour immunity and dormant tumour cells and that these cells develop
specific mechanisms of immuno-escape[3-5]. Tumour dormancy may also result from resistance
to treatment. Many patients that undergo chemotherapy or targeted therapy have received
treatment until progression, as discontinuation of therapy results in disease progression. However,
most of the time (with the notable exception of CML) dormant tumour cells eventually escape
from treatment and lead to relapse. Taken together, these findings present a complex picture of
tumour dormancy. Thus, understanding the mechanisms of relapse must be investigated by a
combination of several fields, which have in common their role in elucidating the long-term
control of tumour cells.
III.3.1.2. METHODOLOGICAL BACKGROUND
Assets of Lille’s teams
Lille's teams have developed an expertise in the field of tumour recurrence and dormancy,
especially in the fields of leukaemia and prostate cancer.
Inserm U837/IRCL builds several experimental models of tumour dormancy. These models are
already available for the different projects and have already led to the discovery of news
mechanisms of cancer persistence. The team is now one of the international leader in this
field.
In collaboration with the molecular biology department of CHRU Lille (Academic Hospital),
Lille team's have focused on the genomic analysis of myeloid malignancies and has
developed large-scale studies in collaboration with national and international clinical trial
collaborative study groups, including ALFA, Phi-LCM, and GFM. This approach has led to the
discovery of the prognostic role of several markers in acute myeloid leukaemia which have
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been quickly translated in the routine. Lille is now the French leader in genomic analysis of
acute myeloid leukaemia, and the molecular biology department performs genomic
screening for several academic and general hospitals in France.
Prostate cancer, which is the prototypal example of tumour dormancy, is studied in Lille
through the original approach of calcium channels at University. This methodology has led to
outstanding publications like Cancer Cell, JCI etc. Prostate cancer is also now studied with
stem cell models at Institut de Biologie de Lille.
Malignant melanoma is a tumour that shows in few cases spontaneous regression and
obvious signs of autologous anti-tumour immunity. This disease is also an attractive model to
study the mechanisms that led to long-term equilibrium between dormant tumour cells and
immune response. Inserm U837 is currently building melanoma dormancy models, and the
dermatology department is one of the top recruiter of melanoma patients in France.
Senescence is a key aspect of the long-term behaviour of resistant and dormant tumour cells.
The Institut de Biologie de Lille has build a competitive team focused on senescence and
oncogenesis.
Highly competitive investigators (see appendix 10)
Program 2 will gather several outstanding invetigators who have developed highly competitive
scientific activivities in their respective fields. For instance, Claude Preudhome, with an h-index at
47 has published 190 papers, most of them as first or corresponding author in high ranking
journals such as New England, JCO, Blood. Leukemia. Natacha Prevarskaya has published in
Cancer Cell, JCI, Nature Review Cancer and is a world class expert in the field of calcium
channel in cancer. Meyling Cheok authored in New England, Cancer Cell, JCI, Nature
Medicine, Nature Genetics, JNCI. Bruno Quesnel published 115 papers in JCO, Blood, Cancer
Research, Oncogene, Leukemia and is involved in both clinical and basic research and is a
recognized expert in the field of tumor dormancy.
III.3.1.3. TEAMS, INSTITUTIONS AND INFRASTRUCTURES INVOLVED IN PROGRAM 2
Research laboratories:
Inserm U837-E3 Head Bruno Quesnel
Inserm U837-E4 Head Pierre Formstecher
Clinical Department of Haematology, CHRU Lille
Clinical Department of Dermatology, CHRU Lille
UMR CNRS 8161 IBL
Inserm U837-E4 Renata Polakowska
INSERM U1003, Université Lille 1, Natacha Prevarskaya
Inserm U837-E5, Guillemette Huet
Translational research poles:
TuDor Biotechnology; CEO Xavier Thuru
Oncovet; Head Dominique Tierny
EA4481 Lille2
Laboratory of cytogenetic Catherine Roche Lestienne
The functional genomic facility of Université Lille 2. Martin Figeac
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Clinical medical departments:
Service des Maladies du Sang, CHRU Lille, Bruno Quesnel,
Service de Dermatologie, CHRU Lille, Laurent Mortier,
Service d'Urologie, CHRU Lille, Arnaud Villers
Human and sociales Sciences departments:
Environment and professional pathologies department, CRDPD EA CHRU, Lille2
III.3.2. MAIN TARGETS OF THE PROGRAM’S WORK
III.3.2.1. BASIC RESEARCH
Objectives
The primary objective of the research program, which will be developed in the Comprehensive
Cancer Centre ONCO Lille is to understand recurrence. The program will specifically focus on
mechanisms contributing to tumour dormancy and relapse after a period of complete remission.
Specific goals
To create new experimental models of tumour dormancy.
To understand basic mechanisms of tumour dormancy
To identify new predictive factors of relapse and translate them into the clinic
To develop new drugs able to target dormant tumour cells and avoid or delay relapse.
General methodology
To understand tumour dormancy and relapse and to test new drugs, new experimental models
must be developed. Working with residual tumour cells from patients is currently an
extraordinarily difficult task because these cells are undetectable in most patients, there are no
well-characterized markers suited for their purification, and they must be studied in an
environment that fully recapitulates host/tumour cell relationships. Our primary goal will be to
establish relevant models using several tumour types. Next, the identified mechanisms of tumour
dormancy will be investigated in a large cohort of patients as ancillary studies of a collaborative
prospective clinical trial. Finally, drugs developed to target mechanisms that allow the long-term
persistence of dormant tumour cells will be tested in experimental models of tumour dormancy
and, if successful, patented and adapted to clinical development. In addition to this integrated
program, we will perform large-scale genomic analyses of tumour samples collected in
prospective clinical trials in order to isolate specific markers that predict relapse.
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Task 1 : Tumour dormancy and immunoevasion
Participants
Inserm U837-E3 Head Bruno Quesnel
Inserm U837-E4 Head Pierre Formstecher
Clinical Department of Haematology, CHRU Lille
Clinical Department of Dermatology, CHRU Lille
Objective : to find new mechanisms of immune mediated dormancy
Led by Bruno Quesnel, Inserm research team U837-E3 has developed a mouse model of tumour
dormancy named DA1-3b in which residual acute myeloid leukaemia (AML) cells are in
equilibrium with the host immune response [4, 6]. Mice in complete remission after one year
manifested less than one thousand or at times less than one hundred dormant tumour cells. Thus,
tumour dormancy in mice can result from a very small population of residual cells that persists in
a balance with the immune system. Using this model, we have identified several mechanisms of
tumour dormancy For instance, dormant tumour cells overexpress B7-H1 immunosuppressive
molecules that inhibit T-cell activity through interaction with PD-1 and B7.1. Dormant tumour cells
also deregulate several pathways, including the JAK/STAT and PI3K/AKT pathways, leading to
cross-resistance between CTLs, TKIs, and chemotherapy[7]. These early results prompted us to
develop additional models of tumour dormancy and to explore possible therapeutic
developments.
New models of tumour dormancy (Carine Brinster): Our current model of tumour dormancy
has led to the discovery of several new mechanisms of long-term persistence, but like other
reported models, it also has severe limitations. The DA1-3b mouse model allowed us to study
the mechanisms of immunoevasion developed by dormant tumour cells. However, few
indications were obtained about the adaptation of the immune system during the period of
tumour dormancy. We are now building an antigen-specific model in which dormant tumour
cells express an artificial antigen. It will allow us to follow specific T-cells in vivo and determine
how the adaptive immune response is modified by the continuous presence of tumour cells.
The results would lead to new strategies of immunotherapy against dormant tumour cells
Extension to solid tumours (Renata Polakowska and Bruno Quesnel): Another important
limitation of the DA1-3b model is that it models dormancy of BCR-ABL leukaemia. It is likely
that some of the mechanisms of tumour dormancy are tumour type-specific [8-9]. To explore
the mechanisms of tumour dormancy in a more general perspective, we are currently
building a mouse model of tumour dormancy in malignant melanoma.
Pathologies
Acute Leukaemia, Chronic Myeloid Leukaemia, Melanoma
Deliverables
(M12) New experimental models of melanoma dormancy
(M24) Antigen-specific models of leukaemia dormancy
(M36) Identification of new immunoescape mechanisms of tumour dormancy
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Task 2 : Tumour stem cells as factors of persistence and relapse
Participants
UMR 8161, IBL : Identification and characterization of prostate cancer stem cells Roland Bourette
Inserm U837-E4 Renata Polakowska
the Cellular Physiology Laboratory INSERM U1003, Université Lille 1, Natacha Prevarskaya
Inserm U837-E5, Guillemette Huet
UMR8161 CNRS, IBL, Martine Duterque
Clinical Department of Dermatology, CHRU Lille, Laurent Mortier
Objectives
Several models have shown that tumour dormancy may be due to the persistence of tumour stem
cells. For instance, in experimental liver tumours, pancreatic tumours and skin papillomas, transient
MYC inactivation induces most tumours cells to differentiate and undergo apoptosis, but some
differentiated tumour cells remain tumorigenic and survive. In CML patients treated for years with
imatinib, long-term complete hematological and cytogenetic remissions result, but BCR/ABL+ cells
persist and can be detected at the molecular level. In patients treated for at least five years,
attempts to withdraw imatinib led to molecular relapses. These persistent tumour cells are leukemic
stem cells, which are resistant to tyrosine-kinase inhibitors. Thus, tumour dormancy occurs even in a
malignant disease that is optimally controlled by continuous treatment because stem cells are not
eradicated. In solid tumours, definitive demonstrations of tumour stem cells are still needed, but
several groups have described a hierarchy of cell types, including some with stem cell properties.
Thus, in many tumours, the dormant tumour cells may be stem cells.
Prostate cancer stem cells (Roland Bourette): Prostate cancer is the prototype of a dormant
tumour. Patients with complete resection of the primary tumour or with non-resectable
malignancies controlled by hormone therapy may carry disseminated tumour cells (DTC) for
years without evidence of clinical progression. Characterization of the factors that control
tumour stem cells in prostate cancer may help to delay tumour progression indefinitely [10].
Roland Bourette, of UMR CNRS 8161, is developing a new experimental prostate cancer stem
cell model. The laboratory of Dr. Larry Rohrschneider (Fred Hutchinson Cancer Research
Centre, Seattle, USA) has generated a transgenic mouse model with the unique property of
expressing GFP in the apparent stem/progenitor cells of the embryonic and adult mouse by
using the stem cell-specific promoter of s-SHIP [11][12]. In collaboration with Dr. Rohrschneider,
Roland Bourette has recently demonstrated that s-SHIP promoter expression is also a marker
for basal epithelial prostate cells exhibiting stem/progenitor cell properties. To pursue the
characterization of PrSC and to extend this study to potential prostate cancer stem cells using
the s-SHIP promoter expression as a marker, this project will be integrated in the SIRIC-Nord de
France. Because of the similarity between stem cell profiles, the identification of regulatory
pathways and specific markers should be useful for multiple tissue systems.
Melanoma stem cells (Renata Polakowska): Another tumour type exhibiting the spontaneous
behaviour of long-term tumour dormancy is malignant melanoma. Patients with metastatic
melanoma may experience spontaneous tumour regression or prolonged dormancy of large
metastases. We have already analyzed the role of the immune response in the control of
melanoma cells in a mouse model (cf. supra). An interesting hypothesis is that the dormant
melanoma cells are stem cells. In collaboration with oncodermatologist Dr. Mortier, we have
initiated the collection of fresh tumours from melanoma patients and have established a protocol
for developing primary melanoma cultures. Our preliminary data has identified new specific
markers of melanoma stem cell that we are currently exploring. A comparative study of the
expression of dormancy markers and stem cells will be undertaken in both human and mouse
melanoma models. [13][14]. Finally, the ability of melanoma and dormant stem cells to escape
immunosurveillance and their sensitivity/resistance to anticancer treatments will be explored.
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Role of intracellular calcium and membrane ion channels in human prostate physiology (Natalia
Prevarskaya).
Prostate cancer is the prototype of dormant tumours. In many patients, the disease remain
quiescent for years before being clinically significant. After radical prostate surgery, even
patients with low PSA level and five years complete remission show DTC in the bone marrow.
In addition, metastatic prostate cancer cells seem to use the same niche than hematopoietic
cells in the bone marrow. These characteristics make this disease an attractive model to study
tumour dormancy and recurrence.
Recent studies have indicated that alterations in calcium homeostasis and in ion channels
could play a central role in the regulation of processes such as proliferation, differentiation
and oncogenesis. Every cell phenotype is characterized by a specific “calcium signature”,
which is dependent on the kinetics, magnitude and sub-cellular localization of calcium
signals. Therefore, quantitative and functional variations of ion channels disturb the
physiological status of the cell and may lead to the development of a pathology called
channelopathy [15]. Accumulating evidence has tended to demonstrate that the
development of some cancers could also involve ion channel aberrations and, therefore,
could be classified as channelopathies. The major scientific project of the Cellular Physiology
Laboratory INSERM U1003 is to study channelopathies in prostate cancer [16-18]. The study of
the role of intracellular calcium and membrane ion channels in the pathophysiology of the
human prostate would help understand the mechanisms of progression in prostate cancer
and escape from tumour dormancy. For this project, we have established two collaborations:
one with Canceropôle Nord-Ouest tumour tissue bank (Pr X. Leroy) and the other with Urology
service of Lille CHRU (Pr. A. Villers) in order to validate our results in human primary cells. We
will also develop a collaboration with Roland Bourette lab in order to test calcium channels
expression and function in prostate cancer stem cells.
Bone metastasis in prostate cancer (Martine Duterque): An important factor of tumour
recurrence is metastatic dissemination. There is now evidence that this process occurs early in
the history of malignancy, and disseminated tumour cells (DTC) may remain quiescent for long
periods before becoming clinically symptomatic metastases. Understanding the metastatic
process will contribute to the comprehension of tumour dormancy. Recently, ETS transcription
factors have emerged as important elements in prostate tumorigenesis because recurrent
translocations involving ETS genes were found in 50 to 80% of prostate cancer cases [19-20]. The
abnormal over-expression of these ETS factors may disturb gene regulation in prostate cells. It is
well established that disseminated tumour cells (DTC) and circulating tumour cells (CTC) exist in
patients in complete remission. These cells are quiescent, related to stem cells and located in
favourable environments, such as the bone marrow. These cancer cells are assumed to mimic
some of the characters of normal cells present in the host organ by expressing genes that are
usually expressed by osteoblasts and/or osteoclasts. This phenomenon, which is called osteomimicry, would apparently allow cancer cells to adapt to the bone marrow environment.
Identifying genes involved in osteo-mimicry could be the subject of therapeutic targeting.
Our goal is to look for a link between “metastatic evolution” and “TMPRSS2-ETS fusion in
primary tumour”. Martine Duterque‟s ERG gene study helped to establish its molecular
transcriptional role and its association with skeletal formation. To achieve the goals outlined
for this project, we have established two active collaborations: i) with the Canceropôle NordOuest tumour tissue bank (Pr Xavier Leroy) and Urology service of Lille CHRU (Arnaud Villers) to
validate our hypotheses and identify genes in a human prostate cancer context and ii) with
the U664 INSERM unit (Philippe Clézardin), experts in bone metastases, to develop mouse
models of the induction of bone metastasis.
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Markers and mechanisms of drug-induced dormancy of colon tumour cells (Guillemette Huet):
Dormancy can be activated by the microenvironment which produces restrictive conditions for
proliferation of metastatic tumour cells. Dormancy can be also a mechanism for surviving
chemotherapy. Entry into quiescence was observed in multiple myeloma with the proteasome
inhibitor bortezomib. A key signalling feature of dormancy induced by microenvironment or
therapy is the low ERK signalling and high p38 signalling that upregulates p53, NR2F1, BHLHB3 and
inhibits c-Jun and FOXM1 (Sosa et al., 2011, Clin. Cancer Res.). Quiescent colorectal carcinoma
cells are still unexplored (Buczacki et al., 2011, Brit. J. Cancer).
Our team has previously studied drug-resistant HT-29 colon cancer cell subpopulations and
clones obtained after chronic exposure to the clinically relevant anticancer agents 5fluorouracil (5-FU) and oxaliplatin (OXA) in terms of metastatic potential and drug-resistance
(Dessein et al., 2011, Cancer Res.). Recently, we have started to study their properties of
cancer stem cells and dormancy in collaboration with another team of our research centre
(Dr R Polakowska). In this project, We will first identify the markers and mechanisms associated
to the induction of quiescence of colon carcinoma cells by 5-FU treatment, and 2- We will
then analyse the expression of the markers identified with the cell model, in samples of human
liver metastases and adjacent liver tissues resected from two groups of metastatic colon
cancer patients (treated or not by neo-adjuvant chemotherapy prior to surgical resection)
Pathologies
Prostate Cancer, Melanoma, Epithelial cancers
Deliverables
(M24) Mouse model of prostate cancer stem cell
(M36) Identification of stem cell characteristics in dormant melanoma cells
(M36) Characterization of calcium channels in prostate and melanoma cancer stem cells
(M24) Identification of drug resistance mechanisms in dormant tumour cells
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Task 3 Tumour dormancy and senescence:
Participants
Team involved: UMR CNRS 8161, Corinne Abbadie, Albin Pourtier
INSERM U837-E3
Objectives: to explore the senescence program in dormant tumour cells
Numerous reports claim that senescence corresponds to an irreversible growth arrest mechanism
that cancer cells have to bypass to generate tumours. However, the cell-cycle arrest associated
with senescence is not irreversible in all cell types, notably in epithelial cells that are at the origin
of the most frequent cancers in humans. Although they display all the characteristics of
senescent cells, normal human epithelial cells that have reached the senescence plateau can
spontaneously reactivate a mitotic process to generate so-called post-senescence (PS)
emerging cells, which are transformed and able to form skin hyperplasias in nude mice. Data
from our group suggest that the oxidative DNA damage encountered by senescent cells could
be the mutagenic motor underlying this neoplastic emergence [22-23]. Therefore, at least in
these cell types, rather than being tumour suppressor, senescence would represent a steadystate, during which cancer-promoting mechanisms occur. Moreover, we and others have shown
that fibroblast senescence is associated with a complete change in the cell secretome. Some of
our current analyses show that this secretome enhances PS emergence and confers new
migratory and invasive properties to the PS-emergent cells.
In the context of tumour dormancy, it must be highlighted that several anticancer radio and
chemotherapies act through the generation of oxidative stress and senescence induction.
Therefore, one can speculate that after an anticancer treatment, some residual tumour cells
may persist in the organism for a long time in a dormant senescent state and that tumour growth
and disease may recur through a mechanism similar to the post-senescence emergence we
have characterized in keratinocyte cultures. For ONCO Lille, we propose to use the in vitro model
of post-senescence emergence of neoplastic keratinocytes to study i) the role of senescenceassociated oxidative stress in the emergence from normal or drug-induced senescence; ii) the
importance of programmed cell death (including apoptosis and autophagic cell death)
resistance acquisition for carcinoma initiation, and the possibility that tumours may acquire this
resistance during normal or drug-induced senescence; and iii) the importance of changes
occurring in the normal or drug-induced senescing microenvironment, notably to the fibroblast
secretome, in terms of promoting carcinoma initiation and conferring malignant properties
Pathologies
Epithelial tumours, Acute Leukaemia, Melanoma
Deliverables
(M36) Identification of senescence mechanisms in dormant tumour cells
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III.3.2.2. TRANSLATIONAL RESEARCH
Task 1 : Predicting relapse
Participants
Inserm U837-E3 Meyling Cheok (Pharmacogenomic)
Laboratory of Haematology CHRU Lille: Claude Preudhomme
Laboratory of cytogenetic Catherine Roche Lestienne
Service des Maladies du Sang CHRU Lille, Bruno Quesnel
The functional genomic facility of Université Lille 2. Martin Figeac
Objective: to find molecular markers predictive of relapse
Understanding the mechanisms of tumour dormancy and relapse require experimental models
to decipher the extreme complexity of these phenomena. A different approach with potentially
faster translation into the clinic is to determine predictive markers of relapse at diagnosis. Claude
Preudhomme has focused on the genomic analysis of myeloid malignancies and has developed
large-scale studies in collaboration with national and international clinical trial collaborative
study groups, including ALFA, Phi-LCM, and GFM. This approach has led to the discovery of the
prognostic role of several markers in acute myeloid leukaemia, such as IDH1 and IDH2, AML1,
and CEBPA [24-27]. The validation of minimal residual markers is also an important part of the
team's work, and it is rapidly translated into the clinic and has led to outstanding publications,
including New England Journal of Medicine, JCO etc. The team has now moved to high
throughput techniques like CGH and SNP arrays and next-generation sequencing (NGS). In
addition, a large tumour bank (Tumorothèque CHRU de Lille) has been filled with every sample
of AML, CML, ALL, and MDS from our region and the national clinical trials for these diseases.
A recent and important development in the project began when Meyling Cheok arrived from St
Jude Hospital (Memphis) with an expertise in the pharmacogenomics of ALL [28-31]. Meyling
Cheok, who received a permanent position in Inserm U837-E in 2009, is now conducting a new
study using transcriptomic analysis of AML cells exposed to cytotoxic drugs. The profile will be
translated into future clinical trials to stratify patients based on primary resistance. It will also offer
leads to be explored in our models of tumour dormancy.
The availability of this recognized expertise and integrated platform will allow us to rapidly
validate the hypotheses raised in our experimental models of tumour dormancy and relapse.
Conversely, the identification of molecular markers that appear to influence the long-term
evolution of myeloid malignancies will be tested in experimental models to understand their
contribution to the persistence of minimal residual disease.
Pathologies
Acute Myeloid Leukaemia, Chronic Myeloid Leukaemia
Deliverables
M12, M24, M36, M48, M60 New predictive markers of relapse in AML and CML
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Task 2 : Targeting dormant tumour cells
Participants
TuDor Biotechnology; CEO Xavier Thuru
Oncovet; Head Dominique Tierny
OCR, Head Dominique Tierny
Inserm U837-E3 Head Bruno Quesnel
Inserm U837-E4 Head Pierre Formstecher
EA4481 Régis Millet Group, leader of pharmaceutical chemistry, and Philippe Chavatte
Group, leader of Drug design, Faculty of Pharmacy
Benoit Rigo EA 4481, Laboratoire de Pharmacochimie, Ecole des Hautes Etudes d‟Ingénieur
EA 4481 Jean-François Goossens “Interdisciplinary Research Group of Therapeutic Innovation”
(director: Pr. J-P. BONTE)
Objective: to design drugs that target immunoescape mechanisms in dormant tumour cells
The objective of this project, in collaboration with a pharmaceutical company [Regis Millet] and
a drug design team [Philippe Chavatte], is to develop small molecules that block the interaction
between B7-H1/B7-1 or B7-H1/PD-1 and allow the restoration of the host anti-tumour immune
response against dormant tumour cells. We have already defined several structures that are
able to interact with B7-H1 and B7.1. We developed in vitro models of resistance to CTLs via B7H1 and B7.1 and an in vivo model of tumour dormancy [Bruno Quesnel]. These models will be
used to evaluate the capacity of the new compounds to restore the immune response and the
capacity of the host to eradicate dormant tumour cells. We hope to develop several molecules
from different chemical families with strong potentials to block the different interactions between
B7.1/B7-H1/PD-1. If successful, these molecules will undergo pharmaceutical development with
the major objective of blocking immunoescape mechanisms in patients in cancer remission and
allowing the eradication of, or at least the long-term control of, minimal residual disease.
Integration of additional teams involved in immunomodulation in cancer into the SIRIC program
will also provide an opportunity to cross-test these different approaches. These approaches
could be tested in all tumour dormancy models developed.
In addition, to this specific project, we will use also our tumour dormancy models to test the
ability of new drugs to eradicate the minimal residual disease. Several pharmaceutical teams
focused on drug synthesis have already a large portfolio of original compounds that will be
tested in these models in a Go/no Go strategy. If successful, compounds will be tested in
veterinarian models with ONCOVET and TuDor Biotech.
Biotech partnership
These therapeutic approaches will be developed in partnership with Biotech Companies
supporting the SIRIC:
TuDor Biotech is a start-up company created by Xavier Thuru and Bruno Quesnel, focused on
drugs targeting dormant tumour cells.
ONCOVET is a veterinary clinic dedicated to the treatment of animal cancers, and as such will
be able to set-up clinical trial to test new drugs against dormant tumour cells.
OCR (Oncovet Clinical Research) is a private Contract Research Organization that proposes
validated animal models of spontaneous diseases.
Xavier Thuru (TuDor Biotech), Bruno Quesnel (Inserm U837-E3), and Dominique Tierny (ONCOVET,
OCR) will elaborate tools to detect minimal residual disease in dog with spontaneous breast
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carcinoma or lymphoma; which mimick human tumour histology and behaviour. Dormant
tumour cells will be isolated from dog‟s bone marrow. This will offer a new model to test new
drugs designed to target dormant tumour cells in clinical trial with large animals.
Pathologies
Acute Myeloid Leukaemia, Chronic Myeloid Leukaemia, Malignant melanoma, Prostate cancer
Deliverables
(M18) Testing new drugs targeting B7-H1 in experimental models of tumour dormancy
(M24)Testing new drugs on minimal residual disease in veterinarian cancers.
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III.3.2.3. CLINICAL RESEARCH
Task 1 : Accelerating the clinical developments of dormant tumour cell-targeting drugs
Participants
Laboratoire d'hématologie CHRU Lille, Claude Preudhomme
Service des Maladies du Sang, CHRU Lille, Bruno Quesnel
Service de Dermatologie, CHRU Lille, Laurent Mortier
Service d'Urologie, CHRU Lille, Arnaud Villers
Objectives
Data from genomic analyses of myeloid malignancies are rapidly accumulating with the
improvement of high throughput techniques like WGS or WES. Validation of these new markers
will be done in clinical trials from collaborative study groups.
If the drug development process from the SIRIC is successful, we will have several dormant
tumour cell-targeting drugs to enter into clinical development. The different clinical departments
of the SIRIC are already strong contributors of large academic- or industry-sponsored teams. This
will facilitate the design of phase I trials.
Pathologies
Acute Myeloid Leukaemia, Chronic Myeloid Leukaemia, Prostate Cancer, Melanoma
Deliverables
(M36) To develop Phase I clinical trials with drugs targeting dormant tumour cells developed
by the Drug design network of SIRIC
(M48) To develop new stratifications in phase III clinical trials of ALFA, GFM, Phi-LMC
collaborative study groups with the molecular and pharmacogenomic markers characterized
by SIRIC's teams.
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III.3.3. EXPECTED RESULTS
To establish Lille as a reference centre for tumour dormancy and predictors of relapse
To develop new drugs that delay or avoid relapse by converting cancer in a chronic disease.
We hope to establish in Lille an internationally recognized center of excellence in the field of
tumor dormancy and relapse. Priority will be given to the testing of hypotheses generated from
one experimental model across other available systems to generate more general and broadly
applicable results (e.g. the role of B7-H1 in tumor dormancy outside the DA1-3b model and the
role of membrane ions channels in drug resistance). Governance through the SIRIC will be critical
for such coordinate effort.
The strength of Lille's research teams in translational research will enable us to reinforce the
current highly competitive activity of predictive markers in myeloid malignancies. Combination
of this already recognized activity with data from pharamacogenomic will allow us to
accurately precise the behavior of the leukemia disease with time and to give the necessary
tools to validate hypotheses obtained in experimental models of tumor dormancy.
The SIRIC will also give us the opportunity to create an entirely new network between
pharmacological, fundamental, and translational teams with biotech companies. This network
will specifically benefit from the coordination by SIRIC as such collaborations between teams
covering such different fields from chemistry to veterinarian models need tight governance. Our
goal is to design and isolate several new drugs targeting dormant tumor cells that could enter
into Phase I trials
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III.3.4. FOCUS ON THE EMERGING RESEARCH ASPECTS THAT MAY BENEFIT FROM FUNDING OF THE
SIRIC
MODELLING RECURRENCE
Nicolas Penel (Centre Oscar Lambret, Universités Lille 2 & Lille – Nord de France)
Several scenarios of post-therapeutic surveillance mechanisms (examination modalities and their
rhythm) will be proposed. The incidence of events of interest accessible to an effective
treatment will be estimated for the different scenarios. Using Monte-Carlo or Markoviens models,
we will gauge optimal conditions of surveillance that maximise the clinical benefit in terms of
quality adjusted life years (QALYs) and that minimise costs to the society (Penel 2008). This
modelling work uses the Bayesian approach (Penel 2009). The factors introduced in the model
(probability of events, management and treatment costs, cost of treating a recurrence, survival
data, quality of life data) will be the purview of the SIRIC. The decision tree diagrams (base-case
analysis) will include data observed in order to estimate probabilities of transition between
different states of health and related costs. Costs will be calculated in the context of the society
(including direct and indirect costs and possibly spot costs arising from the occasion, e.g.
mobilising material resources such as CT scanners or MRI. Survival and quality of life data will be
included in the form of QALYs. The result of the base-case analysis will be subjected to
multifactor analyses of sensitivity involving observed variations of the various elements
introduced in the model. For frequencies and numerical values, the analysis of sensitivity is based
primarily on the Monte-Carlo method and for survival data on Markoviens models. The data
obtained from this modelling work will be a decision-making assistance tool for health policies
and will extend data obtained from randomised clinical trials.
The originality of this modelling work done by ONCO Lille is that much of it will be based on
information gathered from a real population and in a given geographic sector. The usual
weakness of modelling is the use of data obtained from multiple heterogeneous sources such as
clinical trials, retrospective studies or estimations on small samples.
POST TREATMENT REINSERTION
Sophie Quinton-Fantoni (CHRU de Lille, Universités Lille 2 & Lille – Nord de France)
Progress in the treatment of cancers has resulted in a continuing increase in the number of
patients in remission in France (more than 60% of patients are in remission after 5 years, even
though the figures of course depend on the type of cancer, the treatment and the stage of the
disease at which treatment started). Questions of socio-professional insertion and return to work
after treatment are thus being asked more and more frequently. Professional reinsertion is an
important and unanimously recognised factor in the overall management of these patients. It
affects their quality of life, financial security, re-establishing a stable social environment, a feeling
of being normal and control over their lives. The socio-professional consequences of cancers are
undeniably related to the severity of the disease and to its co-morbidities, to the extent of
treatment and its side effects, to the system of social protection, but also to socio-professional
inequalities and psychological, familial, social and professional disparities (work load,
environment, etc.) that determine the capacities of patients to act. In addition, the longer the
employee's sick leave, the more the relation with his work become weaker, and the fewer the
chances of resuming work on good, if not optimal conditions. This is truer since cancer patients
receive little or no information about their work and its resumption.
In the context of "living with" cancer and improving the quality of life of cancer patients, it is
crucial to favour return to work as soon as possible in order to minimise the degradation of
working conditions or a feeling of "not belonging" to the society. At a time when support care is
increasing, there remains inquestionable work to be done in assistance and rehabilitation to
return to work, as shown by the 2009-2013 national Cancer Plan II.
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The Lille occupational medicine team is now working with oncology groups on the issue of socioprofessional reinsertion for breast cancer patients. In addition, the dual competence of our team
in law and medicine (member of the Centre of Law and Perspectives of Law, EA 4487) has
enable it to examine the responsibility of employers concerning the health of their employees at
the international and legal levels; this involves both their obligations of job changes and
reclassification and safety obligations that are a corporate burden in health and workplace
safety.
The aim will be the preparation of a genuine strategy of socio-professional reinsertion by
including its determinants resulting from collaborations with different teams
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III.3.5. APPENDICES
III.3.5.1. PLANNING
2012
MONTHS
1
2
3
4
5
6
7
2013
8
2014
2015
2016
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Scientific program 2: tumour dormancy and persistence
Basic Research
Task 1 : Tumour dormancy
and immunoevasion
Antigen-specific models of
leukaemia dormancy
New experimental
models of melanoma
Stem cell characteristics in dormant
melanoma cells identified
Mouse model of prostate
cancer stem cell
Task 2 : Tumour stem cells as
factors of persistence and
relapse
New immunoescape mechanisms of
tumour dormancy identified
Drug resistance mechanisms
in dormant tumour cells
identified
Calcium channels in prostate and melanoma cancer stem cells
characterizated
Senescence mechanisms in dormant
tumour cells identified
Task 3 : Tumour dormancy
and senescence
Translational Research
New predictive markers of
relapse in AML and CML
Task 1 : Predicting relapse
New predictive markers of
relapse in AML and CML
New predictive markers of
relapse in AML and CML
New predictive markers of
relapse in AML and CML
New predictive markers of
relapse in AML and CML
Task 2 : Targeting dormant
tumour cells
New drugs targeting B7-H1 tested in
experimental models of tumour dormancy
New drugs tested on minimal residual disease in
veterinarian cancers
Clinical Research
Start of Phase 1 clinical trials
with drugs targeting dormant
tumour cells developed by
the Drug design network of
SIRIC
Task 1 : Accelerating the
clinical developments of
dormant tumour cell-targeting
drugs
MONTHS
1
2
3
4
5
6
7
8
Start of development of new
stratifications in phase 3 clinical
trials of ALFA, GFM, Phi-LMC
collaborative study groups with the
molecular and pharmacogenomic
markers characterized by SIRIC's
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
2012
2013
2014
2015
2016
III.3.5.2. BUDGET
K€ HT
2012
2013
2014
2015
2016
TOTAL
EXPENDITURES
Program2 : Dormancy
Staff for the current scientific projects (3 post doctoral
positions)
Equipment
Running
Support for the emergence of new scientific projects
141
420
330
270
320
250
1 590
220
220
200
180
180
1 000
20
140
120
50
330
70
30
30
20
70
20
100
80
50
50
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IV.
National and international collaborations program
IV.1. Role in regional and national clinical research
Lille is funding member of the Cancéropôle Nord-Ouest (CNO) which was set up under the first
“plan cancer I” in 2003. CNO includes the cancer research forces in the four regions of Nord-Pas
de Calais (Lille), Picardie (Amiens), Haute Normandie (Rouen) and Basse Normandie (Caen).
CNO was evaluated by AERES in 2011 and considered as the best canceropole in terms of
added value and granted for the next four years (2011-2014). The five scientific programmes
currently developed by CNO are: “1-From development and validation of prognostic and
predictive biomarkers to therapeutic innovation”, “2Onset and evolution of tumours in malignant
blood disorders”, “3-Multimodality targeting in oncology”, “4-Cancer and Neurosciences” & “5Cancer, Individuals and Society”. More than half of the basic research teams of CNO are
located in Lille, and ONCO Lille cancer research leaders play a key role in the coordination of
CNO programmes (Yvan De Launoit, Claude Preudhomme, Eric Lartigau and Veronique
Christophe in programmes 1, 2, 3 and 5 respectively). ONCO Lille clinicians and researchers
obtained 53 grants from INCa since 2005 (13M €) and are well identified leaders of collaborative
projects supported by INCa in various fields, like:
Christophe Mariette in oesogastric cancers
Philippe Mathurin in hepatocarcinoma
Jean-Louis Lefebvre in head and neck cancers
Claude Preudhomme in translational research on acute leukemias
Bruno Quesnel in tumour dormancy
Natacha Prevarskaya in the growing field of calcium channels and cancers
Fabrice Soncin in angiogenesis
Veronique Christophe in human sciences
Importantly, the cancer register of Lille and its area, created in 2009, is involved in a growing
number of local, regional and national research projects, supported by various institutions:
C2RC, the Regional Cancer Network and Région Nord Pas de Calais for regional projects and
INCa and IReSP (national research institute in public health) for national projects.
Specific collaborations are related to the two scientific programs
For Program 1
Regional organizations for the management of primary liver cancer (networks: CIRRTRANS,
interregional network CARNOR, S Dharancy), oesophageal cancer (OESO data base C
Mariette), lung and mesothelioma cancers (CBNPC 59-62 database A Scheerperel)
Partnership with regional or national scientific societies: FFCD, UNICANCER, FRENCH, SFCD, SPLF,
ERS, IFCT, GORTEC, GETTEC …
A large regional program is ongoing with the radiation oncologists in Nord-Pas de Calais,
Picardie and Champagne Ardennes. This program based on a collaboration with the Aquilab
society (see appendices) will implant strict quality controls in the field of treatment safety and
prostate tumour contouring. This CRNOR program is financed partly by the INCa (one post of
quality officer) and by the Regional Councils.
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For program 2
Creation of a regional Acute Myeloid Leukemia Observatory, bringing together all
oncohematologists working in the Nord Pas de Calais Region (Dunkerque, Boulogne, Arras, Lens,
Valenciennes and Roubaix general hospitals. This observatory collect biological, clinical and
therapeutic data of almost all patients treated for AML in the region. 275 patients have already
been included during the last two years.
Oncohematologists are coordinators or participants in many large-scale studies in collaboration
with national and international clinical trial collaborative study groups, including ALFA, Phi-LCM,
and GFM.
IV.2.
International networks and collaborations
For program 1
Teams involved in program 1 developed numerous bilateral collaborations with national and
international research teams in their individual fields
Main coooperations alre listed below :
International recognition of clinician leading European networks in particular in oesogastric
cancer (C Mariette), liver determinants leading to cancer resistance (P Mathurin, S Dharancy),
tumoral determinants of resistance in head and neck carcinoma (JL Lefebvre) and
mesothelioma (A Scherpereel).
International clinical collaborations based on a strong national leadership and clinical trials
involving EORTC, ELCWP etc…
Partnership with numerous pharmaceutical companies on national and international clinical
trials: Nestle, Merck, GSK, Amgen, Boehringer-Ingelheim, Lilly, Roche, IRIS-Servier, Daichi, EISAI…
For the adaptation of treatment to advanced and recurring tumours, collaboration in imaging is
active with colleagues from Saint Luc University, Brussels (Pr V. Gregoire), Rotterdam (Pr P.
Levendag) and with the two CyberKnife Centres at Mount Vernon Hospital, Northwood and
Royal Marsden London, UK.
Accuray is the first radiation oncology company that manufactures and sells the CyberKnife and
the TomoTherapy systems. Since 2007, Accuray has established a continuing collaborative
partnership with Oscar Lambret cancer centre. Accuray has closely worked with the Radiation
Therapy department for testing and evaluate specified products and technologies under
development for the CyberKnife. Accuray has co-developed with Oscar Lambret cancer centre
an international clinical study with Dr. Mirabel as principal investigator. The study is currently
enrolling patients. Its anticipated end is in 2015. Oscar Lambret cancer centre has developed
and implemented a customer training program for the CyberKnife system and is now one of the
two CyberKnife training centres in Europe.”
Program 2
Teams involved in program 2 developed numerous bilateral collaborations with national and
international research teams in their individual fields (stem cells, dormancy, senescence,
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angiogenesis…). The team working on calcium channels and cancer (Natascha Prevarskaya) is
a member of the recently granted (October 2011) Marie Curie Initial Training network on Ion
Transport Proteins in Control of Cancer Cell Behaviour (IonTrac)
Claude Preudhomme is a member and investigator (WP12 and WP13) of LEUKEMIANET (FP6), a
cooperative network for advancements in leukemia-related research and health care,
associating the leading leukemia trial groups, their interdisciplinary partners (diagnostics,
treatment research, registry, guidelines), industry and SMEs across Europe. He is also a very active
member of European interlaboratory networks investigating the reproducibility of molecular
methods and trying to define standard procedures (IRON study coordinated by Roche
Molecular Biology to evaluate NGS methods, EUTOS network of national and regional reference
laboratories)
Platforms
Occupational medicine: Since the 1990s, partnerships have been developed with colleagues
from Canada in the field of Research on Occupational Integration and the Psychosocial
Environment of Work (Louise St-Arnaud & Anne-Marie Laflamme, Charles de Koninck law faculty,
Université Laval, Quebec). In June 2009, a French-Canadian symposium was held with 400
experts participating.
Oncovet is the coordinator and partner 1 of ANCABOR, a European biotechnology project
supported by the EUROTRANS-BIO 4th Transnational Call published on 7th January 2009. This 3
years project associates 3 academic teams expert in biomaterial conception and evaluation
from France (Inserm U1008 and CNRS UMR8207 in Lille) and Germany (REPAIR-Lab, University of
Mainz), one German SME (Curazan AG) and Oncovet to develop and evaluate functionalized
bioceramic implants liberating anticancer drugs in a spontaneous model osteosarcoma in dogs.
IV.3.
Strategy of the SIRIC for national and international
collaboration
The existing national and international collaborations will be reinforced in all the fields: basic
research, clinical research and technological developments.
A national observatory of oesogastric cancers, including clinical, biological and pathological
data, will be created in the forthcoming year with the support of INCa;
Owing to its visibility in the field in specific cancers (oesophagus, head and neck, mesothelioma
and primary liver cancer), particularly frequent in Lille and its region, ONCO Lille should become
a main player in European clinical trials concerning these cancers
One of our objectives is to create an outstanding and internationally recognized centre of
research on tumour dormancy. To reach this goal, international collaborations at the highest
level will be sought. Bruno Quesnel already started collaboration with mathematicians working
on modelling dormancy at the Center of Cancer Systems Biology (CCSB, Tufts University, Boston,
MA). CCSB hosts one of the world leader groups working on tumour dormancy and is supported
by the NCI Integrative Cancer Biology Program.
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The already existing international visibility of Claude Preudhomme and his coworkers in
translational research on acute myeloid leukaemia will be further developed in the next three
years:
The IRON project will be pursued.
A project focused on the personalized follow-up of residual disease in acute myeloid
leukemia using NGS techniques is in preparation with European partners to apply to the
forthcoming ERA-NET TRANSCAN call for proposals (December 2011).
The Cancer and Leukemia Group B (CALGB), a national clinical research group sponsored by
the National Cancer Institute, will be approached to share data and develop common
projects, in particular in the field of AML in aged patients.
With the specific assets provided by Oncovet and Oncovet Clinical Research (large access to
animals with spontaneous non-induced tumours, canine and feline tissue bank, histological
platform), ONCO Lille Consortium should become a major player in clinical research on animals
with spontaneous tumours. Oncovet Clinical Research ambition for the next five years is to
develop collaborations at both the national and international levels:
Oncovet Clinical Research will enter the national working force on experimental
histopathology and virtual microscopy created in 2011 by the Canceropole Conference and
INCa and propose the creation of an active network involving the complementary forces
available in France in the field of spontaneous tumours animal models.
Oncovet Clinical Research intend to develop research projects with pharmaceutical
companies with EU support (FUI programme) and to start collaborations with the
Comparative Oncology Trials Consortium launched by the National Cancer Institute in order
to better understand the biology of cancer and to assess novel treatments using pet animals
(https://ccrod.cancer.gov/confluence/display/CCRCOPWeb/Home)
Deliverables and planning:
M6 International collaborations Plan Approved
M12 Observatory of oesogastric set up
M12 Frame of the cooperation with comparative Oncology trial consortium defined
M16 Animal spontaneous tumours models international research network set up
M18 first report national and international collaboration
M10 - M58 (one yearly): International Resistance & Dormancy Conference organized
M24, M36, M48 Report on animal spontaneous tumours models international research network
published
2012
MONTHS
1
2
3
4
5
6
7
2013
8
2014
2015
2016
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
National & international collaborations program
First international Resistance
& Dormancy Conference
International
collaborations
Plan approved
International Resistance &
Dormancy Conference
National and international
collaboration first report
Frame of the cooperation
with comparative Oncology
Trial consortium defined
1
2
3
4
5
6
7
2012
145
8
International Resistance &
Dormancy Conference
International Resistance &
Dormancy Conference
Animal spontaneous tumours models
international research network set up
Report on animal spontaneous
tumours models international
research network published
Observatory of oesogastric set up
MONTHS
International Resistance &
Dormancy Conference
Report on animal spontaneous
tumours models international
research network published
Report on animal spontaneous
tumours models international
research network published
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2015
2016
APPLICATION FILE
V.
Partnership and valorisation strategy
V.1. Strategy and priorities
The work handled within ONCO LILLE will give a conclusive opportunity to reinforce the impact
of the research led by the collaborating teams, in terms of academic visibility, industrial
economic and social value for the benefit of the patients,.. Outcomes research and a more
structured clinical management system will improve patient care in the short term and
participation in novel interventional studies is also of potential benefit for the patient.
Besides, the overall objective of the valorisation strategy will be to ensure ONCO LILLE as a
leading European Oncology centre over the next five years.
To meet this priority, the following key strategic actions will therefore be:
1. To transform research investment in IP
2. To develop of an effective partnership strategy with industry
- By reinforcing existing partnerships
- By Developing new partnerships
3. To develop a communication strategy that will enhance the SIRIC‟s attractiveness and
profile
V.2. Strategy implementation
V.2.1. THE TECHNOLOGY TRANSFER ORGANISATION IMPLEMENTED IN THE SCOPE OF ONCO LILLE
Onco Lille will rely on the strong and long lasting partnership and know how already developed
by its mains partners in the field of technology transfer: the SATT Nord de France Valo and
Eurasanté. These bodies will have a clear assignment, aiming to boost the technology transfer
and the economic added value of the Onco Lille research programs
V.2.1.1. THE FRAME OF THE COOPERATION WITHIN LILLE UNIVERSITY HOSPITAL AND CENTRE
OSCAR LAMBRET
A pre-existing collaborative research policy has been built since 1999 between Lille University
Hospital and Centre Oscar Lambret. This strong partnership aims at supporting and developing
collaborative research projects and networks in the field of oncology.
More recently, in 2006, those 2 institutions have created a joint structure named “GCS CRRC” in
order to strengthening their research relationship and promote new innovative projects.
Onco Lille will rely on this experience and know-how in order to establish a support policy, in
close cooperation with the PRES ULNF, the SATT Nord de France Valo and its partner Eurasanté,
aiming to boost promising projects towards the best means of IP licensing and dissemination.
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V.2.1.2. THE FRAME OF THE COOPERATION WITH THE SATT NORD DE FRANCE VALO AND
EURASANTE
Established in January 2009, PRES Université Lille Nord de France was founded by the six public
universities in the region Nord-Pas de Calais and two Graduate Engineering school.The PRES
Université Lille Nord de France gathers 130,000 students, 4,600 researchers and academics, 3000
PhD in six thematic doctoral schools, seven competitiveness poles, many recognized centers of
excellence.
In partnership with the CNRS, PRES ULNF has decided to lump together the existing promotion
structures in a SATT (Société d‟Accélération de Transfert de Technologie) called “Nord de France
Valo”. This new company is being created in association. The SATT will focus on the maturation
steps of the technologies sought to be outlicensed and will also act as a tool devoted to
commercialize those technologies,and also to negotiate the transfer with the industrial partners.
Within the new SATT Nord De France Valo framework, Eurasante will act as a partner of Lille‟s
academic institutions in their process of research valorisation. Eurasanté will operate, on behalf
of this SATT, as a tool for incubation and support the emergence of public/private collaborative
research project.
The ONCO Lille initiative will benefit from the support ofSATT Nord De France Valo, as well as
from Eurasanté, SATT‟s partner for biotechnology and healthcare sector, for the dissemination
and exploitation of its results.
V.2.2. KEY STRATEGIC ACTIONS
V.2.2.1. TRANSFORM RESEARCH INVESTMENT INTO IP
ONCO Lille is committed to creating value through IP rights. The SATT Nord De France Valo and
Eurasante will encourage the creation of a patent portfolio that will give Onco Lille a
technological & market advantage position
Indeed, in order to achieve this goal a valorization advisor will be designated by Onco Lille
partners to detect and follow new projects through the different steps of valorization.
V.2.2.2. DEVELOPING AN EFFECTIVE PARTNERSHIP STRATEGY WITH INDUSTRY
The main goals are to reinforce existing partnerships and to develop new partnerships.
Strong collaborations have been already developed and transformed in a steady flow of
spin-off and industrial cooperations:
ImaBiotech was founded in 2008 after more than 10 years of research initiated by both Pr
Salzet and Pr. Isabelle Fournier in the molecular imaging laboratory (Laboratoire de
Spectrométrie de Masse Fondamentale & Appliquée – EA4550 – Université Lille 1 Sciences et
Technologies). ImaBiotech has developed a platform integrating complementary imaging,
proteomics, and transcriptomics techniques and offers new molecular imaging technologies
to pharmaceutical & diagnostics companies primarily.
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Professor Bruno QUESNEL and Doctor Xavier THURU have both initiated the project TuDOR
BIOTECH, which will be primarily a contract research organisation specialized in preclinical
evaluation of novel anti-tumor agents (Leukemia, immunoescape). The start-up will also
conduct internal R&D based on a strong collaboration with Professor B. Quesnel in the field of
tumor dormancy, thus focusing on the development of new models and the discovery of
drug
response
markers
and
of
novel
therapeutic
agents.
A strong R&D project is on going with Accuray, the society responsible for the development of
the CyberKnife (research contract in 4D evaluation in liver irradiation).
Strong partnerships with pharmaceuticals companies in the field of clinical research
Eurasanté will boost interactions between Onco Lille and economic players aiming at fostering
collaborative R&D&I projects.
Public/Private R&D projects can be backed by different public grant schemes such as 7th
Framework Program grants from the UE, IMI (Innovative Medicines Initiative) from the European
Federation of Pharmaceutical Industries Associations and the European Commission, such as
also France‟s tenders for academia/industry collaborations (FUI projects, Oseo ISI, ANR
programs…).
Eurasanté will assist Onco lille teams in setting up such grants.
Several topics contained in Onco lille research program have already generated interest from
companies:
Company
148
Description
LUNGINNOV
Development of medical devices for in vitro diagnosis and innovative
products to evaluate the endothelial cell dysfunction-associated diseases.
The firsts markets are the sepsis and the cancer.
ISOLIFE
Isolife distributes every day isotopes for nuclear medicine purposes. This
activity requires a performing network to allow rapid deliveries all over the
country. Daily, 70 persons, trained and equipped following ADR regulations,
are involved with the distribution.
ONCOVET
ONCOVET is a private veterinary referral center located in Villeneuve
d‟Ascq (Nord, France) dedicated to diagnostic, imaging and treatment of
spontaneous cancer in dogs and cats. Oncovet has 11 years experience of
these specialized activities and is working with a regional international
network of over 1000 veterinary practionners in France and in the Benelux
countries. The team consists in 10 clinicians and several nurses offering
surgical and cancer treatment facilities. Most of Oncovet clinicians had an
academic clinical or teaching experience before entering the group and
have complementary university diploma in their domain. Oncovet has
been working with different pharmaceutical companies and academic
laboratories for clinical or preclinical research in the field of oncology for
several years.
OCR
The veterinary cancer research center OCR (Oncovet Clinical Research)
develops an innovative activity of clinical research on pets (dogs and cats)
affected by various spontaneously occurring cancers. OCR is a private
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Company
Description
Contract Research Organization that proposes validated animal models of
spontaneous diseases. The private-owned dog can stand for a relevant
model for various cancers: non-hodgkin‟s lymphoma, mammary tumors,
urogenital tumors, bone & soft tissue sarcomas, melanomas, head & neck
carcinomas. Founded in 2010, OCR is a start-up with the “Jeune Entreprise
Innovante” Label and employs 8 qualified experts including 2 PhDs.
OCR is specialized in the design, organisation, monitoring and reporting of
GCP clinical studies on animals. OCR has internal R&D programs focused
on the validation of animal models. Internal laboratory capacities are
available: histology, immunohistochemistry (IHC) managed by a certified
pathologist. For oncology projects, tumours are collected, analysed and
stored in a tissue bank to later identified specific targets of interest. A PhD
project, in collaboration with IRCL (INSERM 837) started in January 2012 on
tumor dormancy.
Maco Pharma
MacoPharma has more than 30 years of innovation in global healthcare,
with expertise in the field of the main leaders in transfusion therapies, with
major innovations contributing to all Stages of Blood Processing.
Innobiochips
Innobiochips provides research to professionals and clinicians with tailormade solutions in microarray technologies, constant back-up, reliable
support and expert advice, whatever the scope of the project.
Intestinal
Biotech
Development
Intestinal Biotech Development is a research service provider with in vitro
and in vivo models investigating in the field of digestive inflammation and
pain like in Inflammatory Bowel Diseases. It develops preclinical studies for
Pharmaceutical, Food Ingredients, and Veterinary companies assessing
anti-inflammatory, analgesic properties, metabolic activities of molecules,
prebiotics or prebiotics, on the digestive tract.
AQUILAB
AQUILAB is a company active in the field of the new Healthcare
technologies. AQUILAB was created in 2000 and focuses on the
development and the marketing of software solutions in Radiology and
Oncology.
LUNGINNOV
Development of medical devices for in vitro diagnosis and innovative
products to evaluate the endothelial cell dysfunction-associated diseases.
The firsts markets are the sepsis and the cancer.
ISOLIFE
Isolife distributes every day isotopes for nuclear medicine purposes. This
activity requires a performing network to allow rapid deliveries all over the
country. Daily, 70 persons, trained and equipped following ADR regulations,
are involved with the distribution.
These companies have expressed their interest and intention of collaboration in letters enclosed
in appendices.
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V.2.2.3. DEVELOPING A COMMUNICATION AND DISSEMINATION STRATEGY THAT WILL ENHANCE
ONCO LILLE ATTRACTIVENESS AND PROFILE: ONCO LILLE AS A LEADING EUROPEAN
ONCOLOGY RESEARCH INSTITUTE
The communication strategy to be developed by the Onco Lille will need to meet two main
objectives:
Building up the credibility of the ONCO Lille: having a specific communication strategy for the
organisation will strengthen its credibility in the eyes of the targeted players i at: businesses,
researchers, other institutes … Different tools will be used in order to disseminate Onco Lille
existence and results such as identity chart ad portfolio, dedicated website, publications,
participation and/or organisation of events. The visibility given to ONCO Lille will then attract
new partners for collaborative research; and foster the participation CARE-IBD project of
relevant national and international experts in.
Ensure a continuous dialogue between all oncology players: In order to address the needs
and problems faced by the oncology sector, the communication strategy needs to aim at
building strong dialogue between all the parties involved in the oncology sector, businesses
and researchers.
V.2.3. LINKS WITH TECHNOLOGY TRANSFER STRUCTURES (SATT)
Established in January 2009, PRES Université Lille Nord de France was founded by the six public
universities in the region Nord-Pas de Calais and two Graduate Engineering schools. It now
includes 30 entities, with: Lille University of Science and Technology (Lille 1), Lille 2 University of
Health and Law, Lille University Charles de Gaulle for humanities, social sciences, literature and
arts (Lille 3), Multidisciplinary Artois University, Multidisciplinary University of the Littoral Opal Coast,
Multidisciplinary University of Valenciennes and Hainaut-Cambresis., Ecole centrale de Lille, École
des Mines de Douai, CHRU Lille university hospital, Oscar Lambret Center, Insitut Pasteur de Lille
and many others.
The PRES Université Lille Nord de France gathers 130,000 students, 4,600 researchers and
academics, 3000 PhD in six thematic doctoral schools, seven competitiveness poles, many
recognized centers of excellence.
Its missions are:
Providing the full range of disciplinary areas, training and research
Structuring the relationship between university projects and policies of local governments.
PRES ULNF has decided to lump together the existing promotion structures in a SATT (Société
d‟Accélération de Transfert de Technologie) called “Nord de France Valo”. This new company is
being created in association with University of Picardie Jules Verne (UPJV, Amiens), University
Reims Champagne Ardennes (URCA, Reims) and CNRS. The SATT will focus on the maturation
steps of the technologies sought to be out licensed and will also act as a tool devoted to
commercialize those technologies, devoted also to negotiate the transfer with the industrial
partners. Within the new SATT framework, Eurasanté will act as a partner of Lille‟s academic
institutions in their process of research valorisation. Eurasanté will act, on behalf of this SATT, as a
tool for incubation and a tool accompanying the emergence of public/private collaborative
research projects. The SIRIC initiative will benefit from the support of this SATT, as well as from
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Eurasanté, SATT‟s partner for biotechnology and healthcare sector, for the dissemination and
exploitation of its results.
V.2.4. LINKS WITH COMPETITIVENESS CLUSTERS
In the Nord-Pas de Calais region, as in other areas of Europe, the challenge of effectively
transferring knowledge toward the industrial sector and the wider society is a major one. It is
addressed by various instruments of which the most recent has been the constitution of pôles de
competitivité (competitiveness clusters). The Nord-Pas de Calais Area contains seven such
nationally recognised clusters involving research teams from the region.
The Nutrition Health and Longevity (NHL) competitiveness cluster gathers, in the Lille area, 80
companies and research institutes in the fields of both nutrition and therapeutic. This NHL cluster
is managed by Eurasanté, a non-profit agency dedicated to economic development for
biotechnology & healthcare in Lille / Nord-Pas de Calais. Eurasanté is also managing an
incubator specialized in the biotechnology and healthcare sector as well as a science park
located at the outskirts of Lille‟s University Hospital Site.
Deliverables:
M6 Frame of the cooperation defined between Onco Lille and SATT/Eruasanté
M12 Promotion and valorization plan approved by Onco Lille
M18 Funds on European projects granted to Onco Lille
M36 M60 Patenting of one patent per year
M 48 M60 Licensing of one patent per year
Planning:
2012
MONTHS
1
2
3
4
5
6
7
2013
8
2014
2015
2016
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Partnership and valorisation strategy
Frame of the cooperation
defined between ONCOLille
and SATT/Eurasanté
Funds on European
projects granted to
ONCOLille
1
2
3
4
5
6
7
2012
151
8
Licence
Licence
Promotion and valorization
plan approved by ONCOLille
MONTHS
Patent
Patent
Patent
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VI.
Knowledge and practices dissemination program
VI.1. Spreading excellence, dissemination knowledge
Communication and results dissemination are essential for a successful achievement of the
project objectives, to protect participant interests and exploitation perspectives as well as to
ensure maximum benefits for the scientific community and the patients. Such activities aim at
generating an effective flow of information and communication about the objectives targeted,
the results obtained during project progress, the contributions made to knowledge and
practices.
ONCO Lille aims to generate numerous outputs, which are expected to be re-used by different
means. An adequate communication and dissemination policy has to be defined and agreed
by the consortium. Such a policy will be based on the following assumptions:
Communication: basic part of dissemination, consisting in raising awareness on the project‟s
aim and objectives, and helping the project to build its identity and profile
Dissemination: widespread publication awareness or extensive promulgation of knowledge
and information generated within the project. 2 types of dissemination are generally
envisaged:
- dissemination for Understanding (targeting groups and bringing them new knowledge
directly, through conferences and main domain events, publications in scientific journals)
- Dissemination for Actions (helping target groups to change practices, through
participation to workshops, training activities)
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Figure 1 : A strategic dissemination plan will be established by the WP X leader, through the following methodology
1
What do we want
to disseminate?
Shared vision and common understanding of what can be disseminated:
1. description of the project
2. knowledge
2
Who are the
stakeholders and
what are we
offering them?
Identification of target audience or groups:
1. internal (employees, managers, supervisory boards, heads of institutions)
2. external (scientific community, citizens)
3. connected (users, other funded projects)
Identification for each of them of the issues the project will help to overcome
3
When do we
disseminate?
Based on project work plan identifying deliverables and milestones
Trying to maintain activities all along project progress (allowing partners being actively
engaged and mobilised through ownership feeling)
4
What are the
most effective
ways to
disseminate?
Match vehicles for dissemination with objectives
Adopt a multi-strand approach to ensure effectiveness of efforts. Explore and evaluate
all available & relevant methods: emailing, newsletter, reports, website, briefings,
workshops, road shows, conferences, one-to-one, media
5
Who might help
us disseminate?
6
How much does it
cost?
Ensure that dissemination activities have been carefully costed once they have been
broken down (avoid surprises)
7
How do we
evaluate the
success?
Put in place suitable mechanisms for reviewing progress and the extent to which the
strategy is meeting our objectives
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Work through existing channels (more profitable than creating further tools)
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VI.2.
Dissemination to the professionals
Organization of knowledge dissemination is already structured between principally the
universities and the CHRU and COL. Additional action will be developed in the framework of
ONCO Lille and the program will be headed by Dr. Sophie Fantoni (CHRU).
VI.2.1. EXISTING DISSEMINATION PROGRAMS
VI.2.1.1. ACADEMIC TEACHING
An integrated education and training program is currently being developed. Indeed, many
courses (DU and DIU) are organized within our institutions (for example, Lille 2 university organizes:
DU Psycho-oncology, DIU Neuro-Oncology, DIU Onco-Urology, DIU Interventional Radiology in
Oncology, DIU External radiotherapy of high technicality). These meetings are the ideal place for
the dissemination of ONCO Lille‟s research results. A partnership with SIRIC‟s researchers will be
made to encourage the rapid transmission of data from ONCO Lille programs to young doctors
in training. A Master degree « Research Biology and Health » organized jointly by Lille1 and Lille2
universities and associating CHRU, COL and research establishments aims to make the future
clinicians aware of medical research but also to train young scientists to research. Scientific
advances will be disseminated to the young practitioners in the framework of this master. As
presented in the project, there is strong interaction with main Universities through all the
graduate and post graduate education programs. LMD programs are ongoing with specific
actions in the PhD field with grants from the Universities, the Regional Council and the Ministry of
Research (Contracts CIFRE).
VI.2.1.2. PROFESSIONAL TRAINING
There is already a wide range of existing training and education in the oncology field. For
example the Oscar Lambret Centre developed an Education and Training Institute in 2008
(Institut de formation Oscar Lambret). In 2009 and 2010 more than 600 postgraduate students
attended over 40 specialised events (42 in 2010) with 32 teachers (Radiotherapy days, palliative
care, PEC Head and Neck, PEC breast, aging, surgery, ...). The majority of participants are from
the inter-regional area (92 %) and most are from private or general hospitals. Strong links already
exist with the outpatients networks (Santelys….). Onco Lille research results could be
disseminated during these courses particularly in sessions concerning pathologies addressed in
scientific programs 1 and 2 and the new practices resulting from Onco Lille‟s work will be
incorporated.
Specific post graduate training workshops are also developed for physicians as the
“radiotherapy days” in January, bringing more than 150 radiation oncologists, physicists and
technician from the region and more largely from France, Spain and North Africa, or the
“surgical workshops” with “live” demonstration in the fields of gynecological and breast
oncology . Training sessions are organized on an international level. For example with Accuray
(CyberKnife Company) for which the COL is training Centre for European and Middle East new
users.
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VI.2.2. TOOLS TO BE IMPLEMENTED
VI.2.2.1. DEVELOPMENT OF MASTER DEGREES
Along already existing masters (for example: Master in Social Law, Master in Clinical and Social
Health Psychology), new actions may benefit from ONCO Lille : the development of a master in
medical physics, an e learning program for the pharmacists around the new molecules in
oncology, a master in oncology nursing and a master in therapeutic education.
1. Master in medical physics:
The Master in medical physics started in September 2010 and has been ranked A in the
preliminary evaluation of its program by the Agence d‟Evaluation de la Recherche et de
l‟Enseignement Supérieur (AERES).
2. Master in oncology clinical research and nursing
Oncology nurses are facing new challenges. The role played by clinical research and the
inclusion of patients in trials mean that trained “clinical research nurses” are needed.
Improvements in care and increased life expectancy for most of our patients bring with them
new questions around training and adaptation of the work to a situation where more patients
are living for longer and expressing new needs and potential new morbidities. ONCO Lille will
provide information on follow-up of patients and will support this specific training (organised
within the framework of the Lille Health Engineering Institute (Institut Lillois d‟ingénierie de la Santé
– ILIS, University Lille 2I), in collaboration with the nursing schools (masters degree)).
3. Master in therapeutic education (Care and autonomy in chronic diseases)
University Lille 1, Lille 2, Lille 3, CARSAT Nord Pas de Calais Picardie
ONCO Lille will support therapeutic education through the development of a master's degree in
coaching and educational therapy in Lille (the university diploma in Patient Education (DUEP)
created in 1998), that will strengthen the training of instructors and program coordinators. The
objective of this diploma is to enable health professionals to coordinate integrated therapeutic
education in the context of adapted care for chronic disease management.
VI.2.2.2. DEDICATED WEB PAGE
1. Web Page
For the dissemination of knowledge and practices, ONCO Lille will create its website with a
system of subscription to a monthly newsletter to better target professionals concerned with
scientific projects. These tools allow professional to keep regularly informed about ONCO Lille
direction and results.
2. E-learning
In 2010, C2RC made the strategic decision to set up an e-learning program dedicated to
training and information. One of the pilot initiatives at Centre Oscar Lambret is aimed at the
pharmacists. Modern medical oncology treatments are based increasingly on oral drugs
(targeted therapies). Such new compounds are radically changing patient care, entailing new
training needs for professionals outside the hospital setting. There are already specific training
activities for nurses and doctors, but few have been organised for pharmacists. E-learning is one
of the possible tools available to bring the information directly to the pharmacy and to achieve
the best response if necessary. Based on strong collaboration between the hospitals and
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universities, this program coordinated by Prof. JL Cazin should start in 2011 and will be evaluated
over the following years. The aim is to transform the SIRIC recommendations (Program 3) into a
strong “e decision making process” at the patient‟s bedside.
VI.2.2.3. ONCO LILLE SCIENTIFIC SEMINARS
The steering committee will organize, one a year, a day of cancer, a scientific meeting about
oncology dedicated to the regional professionals, doctors, researchers and students and
industrials implicated in the project. The seminar will be also open to patient associations with
particular sessions iwhere ONCO Lille advance and results will be popularize and explained to
the patients. The objective is to gather all the players of Tonco
Lille and to assess progress
made on the Onco Lille research.
To complete this meeting, special workshops, more focused will be organized in relation with
axes developed in the scientific programs and it will be the place for exchanges between
scientific researchers, clinicians and HSS researchers.
VI.3.
Dissemination to the patients and the public
VI.3.1. ACTION OF THE REGIONAL COUNCIL “THE WEEK AGAINST THE CANCER”
Because cancer is a leading cause of premature death in our region, it is crucial for the public
not to ignore any solution to better inform, help and support the patients and their families. For
the last 5th consecutive years, the Regional Council and its partners organized a "Cancer Week"
from 15 to 22 November 2011. The week of mobilization is organized in articulation with the
National League against cancer and the “regional plan against cancer”. The Region Nord-Pas
de Calais is committed, alongside the State, in this regional plan against cancer. This week of
mobilization is one of the key actions of this regional plan directed towards patients. Research in
medicine, in the causes of cancers (including alcohol, tobacco), in the factors which may
protect against cancers, in screening reinforcement and patients and family care have been
the themes of the week. This event, unique in France across a whole region, had in 2011
animations in 28 cities of the region with general public animation, shows and public lectures
and discussions and cancer news on local radios. (http://www.semainecancernordpasdecalais.org/programme2011). ONCO Lille, according to the main goals of this week, will be a stakeholder of the
demonstration in reinforcing research on priority cancers of the region, in strengthening the
observation on cancer as tools for decision, in disseminating principal results to professional and
public and in acting on individual and collective determinants and favour the cancer screening.
VI.3.2. COMMUNICATION TO THE PATIENTS
Since 2006, the CHRU along with a number of partners, in particular the Regional Council of
Nord-Pas de Calais has created a telephone desk for responding and assisting patients. It is
implanted in the occupational medicine and professional pathologies department: "SantéEmploi-Info-Services" (SEIS= Health-Employment-Information-Services). This has started from the
complete unawareness of patients of the numerous existing systems and the necessity of
developing large proximity assistance (regardless of place of residence in the region). This is an
innovating regional action with direct links to regional partners with the goal of avoiding socioprofessional marginalisation of people who had cancer treatment, by facilitating access to
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information and by answering legal and/or medical-social-professional questions asked by family
and friends. In terms of operational aspects, this involves orienting people with health and
employment problems to professionals of health and of job preservation/reinsertion, to organize
personalised relations between the professional and the demander and medium-term follow-up
of people benefiting from this service by trained nurses. SIRIC will be an efficient tool to support
of this platform, to develop associated research programs and to conduct actions for the
reinforcement of post-treatment follow-up of patients and favouring the return to work.
Deliverables
M6: Dissemination Strategic Plan approved
M6: WebSite implemented
M12: First E learning course for pharmacists implemented
M21: First promotion qualified Master in oncology research and nursing
M21: First Promotion qualified master in therapeutic education
M12 - M60: Onco Lille seminar organized (one yearly)
Planning
2012
MONTHS
1
2
3
4
5
6
7
2013
8
2014
2015
2016
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Knowledge and practices dissemination
Dissemination
Strategic Plan
approved
E learning course for
pharmacists implemented
2
3
4
5
6
7
2012
157
8
ONCOLille Seminar
First promotion qualified Master in
oncology research and nursing
ONCOLille Seminar
1
ONCOLille Seminar
ONCOLille Seminar
First promotion qualified Master
in therapeutic education
Website implemented
MONTHS
ONCOLille Seminar
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
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2015
2016
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VII.
Organisation and management of ONCO Lille activities
VII.1.
Director
Eric Félix Lartigau
Identity and contact
Date of birth : July 3rd, 1959
Nationality : french
Contact : Centre Oscar Lambret, 3 rue F. Combemale, 59000
LILLE, FRANCE
Mobile : + 33 6 15 42 66 25
Mail : [email protected]
Current position
Director research and co-operations & Chairman, Radiation
Oncology Department , Centre Oscar Lambret, Lille
Short biography
Eric LARTIGAU is currently the President of theFrench Society of Radiation Oncology (SFRO). He has
been vice chairman of the European Network for medical radio-Isotope and beam research (EMIR)
(2001-2002), General Secretary of the European Society for Therapeutic Radiology and Oncology
(ESTRO) 1997-2003, Member of the « New treatment committee » E.O.R.T.C., 1997-1999 and
Secretary of the European School of Oncology (E.S.O.) French expression 1996-1998. He is an expert at
the “International Atomic Energy Agency” (IAEA). Eric Lartigau recieved his Medical degree in 1988, his
PHD Thesis in Sciences – European Label (Paris-Sud University) in 1994 and is Professor in Radiation
Oncology (Lille 2 University – France) since 1999. He has various diplomas and a University Degree in
Health Economics (Paris VI University – France) in 2000.
Research Activity
At the regional level is the coordinator of the “Axis III Cancéropôle Nord-Ouest: Multimodality targeting
in Oncology”. He published
 140 articles (pub med)
 34 books and chapters
 470 summary and presentations
Role in ONCO Lille
Eric Lartigau will be responsible for the scientific and medical aspects of the ONCO Lille project. He will
represent the project in all situations and will be responsible for promoting its work.
He will chair the Scientific Steering committee and oversee the development of the scientific strategy
and plans. He will be in charge of implementing ONCO Lille action plan and preparing the scientific and
medical programs. He will supervise the coordinating team, thus overseeing the performance of the
ONCO Lille’s research and work programs.
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VII.2.
Administrative and Managerial organisation
VII.2.1.
ONCO LILLE PROJECT GENERAL STRUCTURE
The two funding members of the SIRIC ONCO Lille Project are the academic Hospital, the CHRU
and Centre de Lutte contre le Cancer, the COL, which are formally joined together in a
Healthcare Cooperation Group since 2005, the GCS Centre Régional de Réference en
Cancerologie, also known as C2RC.
Associate members ((listed below) will join the SIRIC project through the signature of a
consortium agreement that will allow them to take part in the management of the project. The
structure of a legally formed consortium is particularly suitable, as it provides a joint decisionmaking structure to guarantee the quality of the scientific strategy.
Founders
Lille University Hospital (Centre Hospitalier Universitaire)
Oscar Lambret Cancer Centre
Associate members
Science and Technology Faculty, Université Lille 1
Law and Health Faculty, Université Lille 2
Human and social sciences, Université Lille 3
Institut de Biologie de Lille
CNRS
INSERM
The other partners will be associated in a more punctual way to evaluate the scientific and
financial results of the SIRIC ONCO Lille project, through a steering committee
Partners
Lille Nord de France Research and Higher Education Cluster, PRES
Lille Cancer Research Institute
Institut Pasteur de Lille
Lille Nord de France MESHS (European Social sciences Centre)
Eurasanté economic interest group
The Faculty of Medicine of Lille
The Faculty of Pharmacy of Lille
The Faculty of Odontology of Lille
The League against Cancer (Cancer Research Association)
Fédération universitaire polytechnique de Lille (Lille higher education federation)
Groupement Hospitalier de l‟Institut Catholique de Lille (University and Hospitals)
Armentières General Hospital (Centre Hospitalier d‟Armentières)
Roubaix General Hospital (Centre Hospitalier de Roubaix)
Seclin General Hospital (Centre Hospitalier de Seclin)
Conseil Régional du Nord Pas de Calais
Lille Métropole Communauté Urbaine
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ONCO Lille will be managed by simple and efficiency-oriented governance, fulfilling all the
crieria of a good governance system
Efficiency: all decisions need to be taken in the timescale of the project and with all the required
autonomy and flexibility in order to decide on strategic issues and implement the project
Transparency: all decisions must be taken regarding a clear and opposable process with a full
motivation of the decisions
Balance of the power: all decisions must be taken to the right level so as to avoid any possible
conflicts of interest
Simplicity: clarity of the system
Risk management: the decision making process must be thought outin order to avoid any risk
on the implementation of the project
Openness to others stakeholders like the society, business partners and international
cooperations
ONCO Lille governance will be implemented through three levels of management and three
authoritative bodies, which are summarized in the schema below. This organization will provide
the operational flexibility required to guarantee the decisions on strategic and operational issues
and a close and transparent examination of the rigour in the management, of the scientific
results achieved and the use of the funding granted to this organisation.
The first level is the governance of ONCO Lille, which will rely on two authorities: the board of
directors (BD) and the International Scientific Council (ISC).
In close cooperation with the BD and the ISC, the second level will be the management of the
project run by the Director and his staff.
The last level is the scientific organisation and management: it will be implemented through the
various WP.
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VII.2.1.1.
STRATEGIC AND GOVERNANCE MANAGEMENT:
Board of Directors
Comprising 9 members, ONCO Lille‟s Director and General Secretary and one observer, the BD is
the operational strategic and formal decision-making body of the project. The role of the BD is
decision making regarding priority issues like budget, distribution of the funds between WP,
guidelines in research, clinical, technology transfer, collaborative research, training… areas and
the launching of new programs. It will have the power to name the director of the project.
It will be in charge of the strategic policy, revolving around key goal settings in order to enable
the progress of research programmes in the frame of the determined timescale.
The BD will approve the long term strategy and annual implementation plans of the scientific
programmes. It frames and votes the annual budget based in particular on the distribution of the
INCA grant and on the members financial contributions. It is in charge of any amendments to
the Consortium Agreement and it decides to accept, reject or exclude members in the
consortium.
It also determines the SIRIC strategy in terms of research, communication and dissemination of
results.
The BD is made up of the founding institutions as well as the associate members of the
consortium, the Director and the General Secretary. One member is invited as an observer: the
President of the Cancéropôle Nord Ouest. It meets annually 3 times a year in January, May and
November.
The provisional composition of the Board of Directors is:
CHRU : Yvonnick Morice
COL : Bernard Leclercq
C2RC: Françoise Weingertner
Science and Technology Faculty, Université Lille 1 : Philippe Rollet or representative
Law and Health Faculty, Université Lille 2 : Pr Christian Sergheraert or representative
Human and social sciences, Université Lille 3: Mr Jean-Claude Dupas or representative
Institut de Biologie de Lille : Yvan Delaunoit
CNRS : Françoise Paillous
INSERM : Samir Ould Ali
Director : Eric Lartigau
General secretary : to be recruited
Two groups of trustees will be set up: one from the founding partners with the majority of voting
rights, one with associated members
General Assembly
Once a year, a General Assembly uniting the founders of the associate members and the
partners (22 members) will take place in December.
Just preceded by the International Scientific Committee in November, the General Assembly has
a task to present to ONCO Lille‟s supports and partners the achievements of the past year in the
realm of scientific results as well as project management, budget and daily management.
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VII.2.2.
INTERNATIONAL SCIENTIFIC COMITTEE
Formed by 4 international experts, ISC will be appointed by the BD. The ISC‟s mission is to advise
BD and the steering scientific committee on research and clinical matters and to provide critical
judgments on the work performed in the frame of SIRIC research, translational and clinical
programs. This committee will assess the annual achievements regarding the goals that were set
and ultimately patient benefit. It will have a powerful and important role by providing critical
advice and constructive proposals, with each year the delivery of an independent report.
Members of the ISC are appointed for the duration of the project.
The ISC meets once a year in November, except the first year, during which he will also approve
the scientific strategy and plans around 3 months after the beginning of the project.
The ISC will comprise 4 distinguished scientists:
Michel Coleman, Professor of Epidemiology and Vital Statistics, Cancer Research UK Cancer
Survival Group, London, UK
Riccardo Fodde, Department of Pathology, Erasmus MC, Rotterdam, The Netherlands.
Michael Molls, Professor and Chairman of the Department of Radiation Oncology, Technische
Universität München, Germany
Jan Vermorken , Department of Medical Oncology, Antwerp University Hospital, Belgium
VII.2.2.1.
MANAGEMENT OF
ONCO LILLE
The operational management level will manage the project on a daily basis. The director and
the general secretary will have the task to detail the setup of the framework, implement BD
decisions on administrative, human resource and financial matters, changes in allocation of
resources, time schedule follow-up, and dissemination and communication actions. It will have
liabilities regarding BD and ISC: preparing the BD and ISC meetings, giving clear and fair
information, implementing the decision.
Particularly, the operational management level will be tasked with:
The implementation of the strategic policy defined at the strategic level
The general management of the project
The implementation of the scientific programs
The preparation of the budget and of the financial allocations
The Director
The director is responsible for the scientific and medical aspects of ONCO Lille. He especially
oversees the implementation of ONCO Lille‟s scientific strategy and action plan. He represents
the SIRIC in all situations and is responsible for promoting its work.
The Director chairs the Scientific Steering Committee (see below).
Together with the General Secretary, he supervises the coordinating team, thus overseeing the
performance of the SIRIC‟s research and work programs.
The Director is appointed by the BD.
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The General Secretary
The General Secretary oversees the day-to-day running of the SIRIC as he is fully devoted to this
mission. He prepares the items for discussion by the BD, in particular the draft annual budget,
which he is responsible for implementing.
The General Secretary is the line manager for the policy officers and makes proposals for
recruiting these staff members. Under the Director‟s authority and in liaison with the scientific
steering committee, he contributes to promoting the SIRIC‟s activities.
The General Secretary is recruited by the C2RC and he‟s appointed by the Board of Directors.
The permanent team
The management of ONCO Lille will benefit from the recruitment of a qualified permanent staff,
thus ensuring the continuity of its actions.
The permanent team will be composed of 2 full time staff under the supervision of the director of
ONCO Lille and of the General Secretary for the administrative part:
1 scientific project manager: he will be in charge of the organisation and management of
scientific projects in collaboration with work package leaders (from methodological set up to
implementation). He will also deal with partnerships, communication, knowledge and
dissemination practices
1 financial expert (0.5 part time) in charge of proposing the annual budget draft and
monitoring of its use.
1 administrative assistant (0.5 part time) to assist the General Secretary.
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VII.3.
Scientific organisation and management
The management of each work package presented below is assigned to one leader, who is
responsible for the achievement of the annual action plan and for the quality of the projects
conducted within his WP. The permanent team will support each work package leader in dayto-day activities.
The coordination of the activities is assured by a monthly meeting with each work package
leader.
Management and organisation – E. Lartigau
INTEGRATED RESEARCH PROJECT
Program 1
National and
international
collaborations
program
Resistance
C. Mariette
Program 2
Human and Social
Sciences
V. Christophe
Dormancy
B. Quesnel
Platforms
P. Formstecher
Biology
Imaging
Animal
models
Y. De
Launoit
Clinical
research and
methodology
I. Fournier
D. Tierny
A. Duhamel
Industrial
Partnerships &
valorisation
program
SATT –
Eurasanté
A. Coilliot
Knowledge and practices dissemination program – S Fantoni
WP 1 aims to set up the management and governance frame. It will be run by the director of
the project, in close cooperation with the BD. It also includes the management of the
contractual (consortium agreement), financial, regulatory and ethical aspects of partner
projects.
WP 2 and 3 represent the core of the ONCO Lille program. They are scheduled in a five years
time frame on a multidisciplinary basis. The organization of the WP intends to foster the
emergence of new projects and strengthen the implementation of the current portfolios
project as well. The leaders of the WP will aim to create the necessary conditions for sharing
knowledge and developing innovative practices (therapies, markers..) throughout the
duration of ONCO Lille.
WP 4 aims to foster the contribution and the interaction between human and social sciences
and the scientific programs.
WP 5 and 6 will be implemented in order to manage the access of the portfolios of the shared
integrated platform for the two scientific programs throughout the duration of ONCO Lille
WP 7 and 8 aim to develop the international and national cooperation of ONCO Lille while
WP8 intends to foster the cooperation with the private sector in order to bring the innovation
developed under the ONCO Lille umbrella to the market on the one hand and to develop
the cooperation in areas such as clinical trials or training on the other hand.
WP 9 focuses on knowledge and dissemination.
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VII.3.1.
SCIENTIFIC STEERING COMMITEE
The SIRIC‟s Scientific Steering Committee is made up of the programme leaders, of the platform
and work package leaders, of the Director, the General Secretary and the permanent team of
the ONCO Lille programme.
It meets monthly, around 10 times a year. It is chaired by the Director.
The Scientific steering committee will be in charge of the management of ONCO Lille
programmes. It will act as both a discussion and planning body and an evaluation body.
It will present the research and action programs to the Board of Directors, and in particular how
they will be broken down into individual projects and activities within a multiannual framework,
with outcome objectives and criteria. It will then evaluate the scientific feasibility and coordinate
the implementation of the scientific programmes as well as the necessary interface with partner
institutions. It will also assess the projects and actions after they have been carried out, and in
particular whether the expected outcomes have been achieved.
VII.3.2.
MANAGEMENT TOOLS TO BE IMPLEMENTED - ACTION PLAN
The steering mechanism of the ONCO Lille programs will be implemented according to project
management methodologies. Both scientific programs and actions will be formalised through an
operational management tool: the Master Plan. This tool illustrates the development of a work
program through its key stages and main deliverables, linked to a multi-year calendar, until 2016.
Some deliverables have already been identified for scientific programs, organisation and
management, national and international collaboration, valorization strategy, and knowledges
and practices dissemination (see the relevant chapters).
Once certified, our first task will be to update and validate this materplan within the board of
directors.
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Deliverables
M1 : Consortium agreement signed by SIRIC Partners
M2: Internal regulations and by-laws of the consortium defined
M1: first scientific steering committee (10/year)
M2: Meetings schedule established
M3: Permanent team recruited
M3: First International Scientific Committee to define scientific strategy (1/year)
M4: Masterplan proposed by the steering committee
M4: First board of directors to approve the strategy and the Masterplan
Masterplan
2012
MONTHS
1
2
3
4
5
6
7
2013
8
2014
2015
2016
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Management & organisation
Consortium agreement signed by ONCOLille Partners
10 scientific steering committes / year
First scientific steering committee
Last scientific steering
committee
Internal regulations and by-laws of the consortium defined
Meetings schedule established
5th international
Scientific Committee
Permanent team recruited
First international Scientific Committee:
scientific strategy defined
4th international
Scientific Committee
3rd international
Scientific Committee
2nd international
Scientific Committee
Action Plan defined
Board od director : 3 time / year
First board of directors : strategy and
Action Plan approved
MONTHS
1
2
3
4
5
6
7
2012
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8
Last board of directors
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VIII.
Budget
VIII.1.
ONCO Lille operating previsional budget
The amount of finding requested for the SIRIC project comes to 7, 700 million Euros over 5 years.
This funding will enable to develop further transversal interactions, to sustain emergent programs,
to initiate large scale collaborations and to finance program parts not achievable with the
current amount of funding obtained by SIRIC researchers through the different grants.
K€ HT
2012
2013
2014
2015
2016
TOTAL
EXPENDITURES
Equipment
Staff
Running
TOTAL EXPENDITURES
390
0
0
365
0
755
1 120
1 120
1 100
955
955
5 250
330
340
335
330
360
1 695
1 840
1 460
1 435
1 650
1 315
7 700
1 840
1 460
1 435
1 650
1 315
7 700
REVENUES
INCa grant
Equipment
Staff
Running
TOTAL REVENUES
390
0
0
365
0
755
1 120
1 120
1 100
955
955
5 250
330
340
335
330
360
1 695
1 840
1 460
1 435
1 650
1 315
7 700
In addition to the INCa Grant, the founders and the associate members will provide skilled
workforce to the benefit of ONCO Lille through the provision of working time from the program
leaders, the platform and work package leaders and from all the scientists dedicated to this
project.
The valuation of this involvement of the partner institutions reaches the amount of 2,000 000€ and
will allow the implementation of the scientific programs throughout the duration of ONCO Lille.
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K€ HT
2012
2013
2014
2015
2016
TOTAL
EXPENDITURES
Management and governance
150
150
150
150
150
750
Staff (general secretary, scientific coordinator, 1/2 financial
technician and 1/2 administrative assistant)
150
150
150
150
150
750
Program 1 : Resistance
475
375
400
475
375
2 100
Staff for the current scientific projects
Equipment
Running
Support for the emergence of new scientific projects
275
100
25
75
275
275
275
25
75
50
75
275
100
25
75
25
75
1 375
200
150
375
Program2 : Dormancy
420
330
270
320
250
1 590
220
220
200
180
180
1 000
20
140
120
Staff for the current scientific projects (3 post doctoral
positions)
Equipment
Running
70
30
30
20
70
20
Support for the emergence of new scientific projects
100
80
50
50
50
330
Platform 1 : Biology
200
150
150
150
100
750
Staff for the current scientific projects
Equipment
150
50
150
150
100
50
100
650
100
Platform 2 : Imaging
300
200
200
250
150
1 100
Staff for the current scientific projects
200
200
200
150
150
900
Equipment
100
100
200
Platform 3 : Animal Models
90
50
50
75
50
315
Staff for the current scientific projects
50
50
50
50
50
250
Equipment
40
Platform 4 : Clinical research and methodology
25
65
105
75
75
70
50
375
Staff for the current scientific projects
75
75
75
50
50
325
Equipment
30
National and international collaborations
20
40
50
50
60
220
Running
20
40
50
50
60
220
Industrial partnerships and promotion
50
60
60
70
80
320
Running
50
60
60
70
80
320
Dissemination of knowledge and practices
30
30
30
40
50
180
Running
30
30
30
40
50
180
1 840
1 460
1 435
1 650
1 315
7 700
TOTAL EXPENDITURES
K€ HT
2012
20
2013
2014
2015
50
2016
TOTAL
REVENUES
External contributions
1 840
1 460
1 435
1 650
1 315
7 700
INCa grant
1 840
1 460
1 435
1 650
1 315
7 700
1 840
1 460
1 435
1 650
1 315
7 700
TOTAL REVENUES
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VIII.2.
Funding from the SIRIC call to the scientific programs
The ONCO Lille grant will fund mainly the two integrated research programs and the platforms
required to perform the work up to7.7million € over 5 years, representing almost 80% of the total
budget.
The funding (2.1 millions€) of Program 1, dedicated to tumour and host resistance to loco
regional treatments, will be mainly (83% of the total funding for the program) use in order to
support the recruitment of personnel staff for the current scientific projects stimulating the
emergent new scientific project
Program 2, dedicated to tumour dormancy and persistence will be drive by the same goal :
empower the capabilities for Onco Lille to perform current scientific projects and develop
new scientific project by the hiring of highly skilled staff (83%of the total funding for the
program)
Infrastructures and platforms: A substantial part of the INCA grant will be attributed to the four
integratedPlatform:
2.4 million€ (31% of the total INCA grant). This funding will be used mainly to support highly
research and technical staff.
VIII.3.
Funding of the SIRIC call for management, collaboration,
valorisation, and dissemination
9% of the budget will be devoted to coordination and governance of the project, for the
recruitment of a general secretary, scientific coordinator, 1/2 financial technician and 1/2
administrative assistant.
Respectively, 220k€, 320k€, and 180 k€ will be necessary for the national and international
collaborations industrial partnerships and the valorisation as well as the dissemination of
knowledge and practices
VIII.4.
Funding already obtained by SIRIC researchers:
The researchers of SIRIC have obviously obtained financing on the existing projects from the
INCa but also from other funders:
The total amount of the other funding collected for the 2006-2011 period amounts up to 26 523
700 million €. These funding do not take in account the costs of the permanent research
personnel working in the basic, translational and clinical sites of the SIRIC (which it is detailed in
paragraph XXX).
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Per program or platform from 2006 to 2011, these funding are distributed:
Scientific Program 1:
Scientific Program 2:
Platform Biology:
Platform methodology and clinical research:
Platform Imaging:
HSS projects:
9 projects
19 projects
100 projects
10 projects
49 projects
33 projects
6 829 000 millions €
2 615 000 millions €
8 644 500 millions €
1 277 000 millions €
5 078 000 millions €
2 080 700 millions €
The part of INCa funding is 7 940 000 million€ so about 30% of the total and the main other
financing bodies for the SIRIC programs representing 18 583 700 million € include:
The regional and national public funding bodies: CNRS, Inserm, ANR, CNO, Lille1, Region…
Associations: ligue contre le cancer, ARC, FRM, Fondation de France…
European granting
Partnerships with pharmaceutical companies Sanofi, Merck, Fabre, Medicen, Oseo, Novartis,
Teva, Roche…
Moreover, funding from the regional council through FEDER (European Union) and/or CPER
(Region) grants have been already obtained on SIRIC specific programs showing the strong
support of Region in the SIRIC project:
V. Christophe - HSS
J. Foncel - HSS
S. Fantoni - HSS
N. Reynaert – scientific program1
B. Quesnel- scientific program 2
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SIRIC - CALL FOR APPLICATIONS 2012
124 K€
127 K€
55 K€
100 K€
276 K€
Call for applications 2012
Certification of sites dedicated to integrated
research in cancer
- SIRIC -
Consortium ONCO Lille
Administrative part
Nom de l’établissement candidat
C2RC Lille
CHRU & Centre Oscar Lambret
Nom du directeur du projet SIRIC
Pr. Eric Lartigau
Etablissements partenaires
CHRU of Lille
Centre Oscar Lambret
Université(s) de référence
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PRES Lille Nord de France
ADMINISTRATIVE PART
C
O
N
T
E
N
T
1. Fiches signalétiques
173
2. Engagements et Signatures
175
2.1.
2.2.
2.3.
2.4.
172
Directeur du projet SIRIC
Etablissement candidat
Engagement et signatures des universités de référence
Engagement et signatures des partenaires
SIRIC - CALL FOR APPLICATIONS 2012
175
176
177
180
ADMINISTRATIVE PART
I.
Fiches signalétiques
Directeur du projet SIRIC
Nom et prénom du directeur du projet SIRIC :
Eric LARTIGAU
Adresse de correspondance :
Département
Universitaire
de
Radiothérapie
Centre
Oscar
Lambret
3, rue F. Combemale - BP 307 - 59020 Lille Cedex,
France
Email :
Téléphone :
[email protected]
03 20 29 55 95
Structures administratives de rattachement:
Centre Oscar Lambret,
Centre Hospitalier et Universitaire de Lille, Faculté de
Médecine Henri Warembourg, Université Lille2,
Université Lille Nord de France
Etablissement candidat
Bénéficiaire du financement de l’INCa
Nom de l‟établissement :
Centre Hospitalier Régional Universitaire de Lille et
Centre Oscar Lambret – GCS C2RC
Nom du directeur :
représentant légal -personne habilitée à signer la
convention
Email :
[email protected] 03 20 29 55 51
Téléphone :
[email protected] : 03 20 44 41 43
Adresse :
CHRU de Lille, 2, avenue Oscar Lambret –
Mr Y Morice et Mr B Leclercq
59 037 Lille Cedex, France
Centre Oscar Lambret, 3, rue F. Combemale - BP 307 59020 Lille Cedex, France
si différent du représentant légal
Personne habilitée à signer la convention,
Nom prénom :
Titre et fonction :
Nom du site d‟accueil hospitalier
(si applicable)1 :
Nom prénom du directeur du site d‟accueil
(si applicable) :
Adresse de correspondance :
e-mail :
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SIRIC - CALL FOR APPLICATIONS 2012
Centre Hospitalier Régional Universitaire de Lille
ADMINISTRATIVE PART
Etablissements partenaires
Nom de l’établissement :
Adresse :
Nom du directeur de
l’établissement/représentant légal :
Centre Hospitalier Régional
Universitaire
2 avenue Oscar Lambret
59037 Lille
Mr Yvonnick MORICE
Centre Oscar Lambret
3 rue frédéric Combemale
BP307 – 59020 Lille cedex
MR Bernard LECLERCQ
Institut de Biologie de Lille
CNRS
INSERM
1 rue du Pr Calmette
BP447
59021 Lille cedex
2 rue des canonniers
59800 Lille
1 place de verdun
59000 Lille
Mr Yvan DE LAUNOIT
Mr Jean-Benoît BUBURCQ
Mr Samir OULD ALI
Universités de référence
Nom de l’université :
Pôle
recherche
et
d‟Enseignement Supérieur Lille
Nord de France (PRES Lille
Nord de France)
Université des Sciences et
Technologies de Lille
Lille 1
Université Droit et Santé
Lille 2
Université Sciences Humaines
et Sociales
Lille 3
174
Adresse :
Nom du président de l’université:
1 bis rue Georges Lefèvre –F59044 Lille
Pr Christian SERGHERAERT
Cité Scientifique 59655 Villeneuve
d'Ascq Cedex
Mr Philippe ROLLET
42, rue Paul Duez 59000 LILLE
Pr Christian SERGHERAERT
Domaine Universitaire du Pont de
Bois, BP 60149, 59653 Villeneuve
d'Ascq, Cedex
Pr Jean-Claude DUPAS
SIRIC - CALL FOR APPLICATIONS 2012
ADMINISTRATIVE PART
II.
Engagements et Signatures
II.1. Directeur du projet SIRIC
Signature du directeur du projet SIRIC
Nom et prénom du directeur du projet SIRIC:
Eric LARTIGAU
Signature :
Fait à Lille, le 9 décembre 2011
Signature du représentant légal de ou des établissements de rattachement du directeur
du projet SIRIC
Nom de l‟établissement:
Centre Hospitalier Régional Universitaire de Lille (CHRU)
et
Centre Oscar Lambret (COL)
Après avoir pris connaissance de l‟appel à candidatures « Labellisation de Sites de recherche intégrée sur le
cancer » et du présent dossier de candidature,
Nous, soussignés, Yvonnick Morice, en qualité de Directeur général du CHRU de Lille, Bernard Leclercq, en
qualité de Directeur général du COL,
- avons pris bonne note de la mission du directeur et l‟autorisons à mener cette mission
Signatures :
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SIRIC - CALL FOR APPLICATIONS 2012
Fait à Lille, le 9 décembre 2011
ADMINISTRATIVE PART
II.2. Etablissement candidat
Signature du représentant légal de l’établissement bénéficiaire du financement INCa
Nom de l‟établissement:
Centre Hospitalier Régional Universitaire de Lille (CHRU)
et
Centre Oscar Lambret (COL)
Après avoir pris connaissance de l‟appel à candidatures « Labellisation de Sites de recherche intégrée sur le
cancer » et du présent dossier de candidature,
Nous, soussignés, Yvonnick Morice, en qualité de Directeur général du CHRU de Lille, Bernard Leclercq, en
qualité de Directeur général du COL,
certifie l‟exactitude des informations présentes dans ce dossier ;
m‟engage à mettre en œuvre les activités décrites dans ce dossier de candidature, et à transmettre un
rapport périodique d‟activité sur l‟état de ces différentes actions;
- m‟engage à mobiliser intégralement les crédits obtenus sur le projet précité dans les meilleurs délais.
Signature :
176
SIRIC - CALL FOR APPLICATIONS 2012
Fait à Lille, le 9 décembre 2011
ADMINISTRATIVE PART
II.3. Engagement et signatures des universités de référence
Nom de l’université: Université des Sciences et Technologies de Lille (Lille1)
Nom du président de l’université: Mr Philippe ROLLET
Après avoir pris connaissance de l‟appel à candidatures « Labellisation de Sites de recherche intégrée sur le
cancer » et du présent dossier de candidature,
je soussigné, Mr Philippe Rollet,
m‟engage à soutenir et à accompagner les activités du SIRIC telles que décrites dans ce dossier de
candidature,
a pris connaissance du fait que mon établissement devra finaliser un accord de consortium avec les
partenaires et l‟établissement candidat.
Fait à Lille, le 9 décembre 2011
Signature :
177
SIRIC - CALL FOR APPLICATIONS 2012
ADMINISTRATIVE PART
Nom de l’université: Université Droit et Santé (Lille2)
Nom du président de l’université: Mr Christian SERGHERAERT
Après avoir pris connaissance de l‟appel à candidatures « Labellisation de Sites de recherche intégrée sur le
cancer » et du présent dossier de candidature,
je soussigné, Mr Christian SERGHEREART,
m‟engage à soutenir et à accompagner les activités du SIRIC telles que décrites dans ce dossier de
candidature,
a pris connaissance du fait que mon établissement devra finaliser un accord de consortium avec les
partenaires et l‟établissement candidat.
Fait à Lille, le 9 décembre 2011
Signature :
178
SIRIC - CALL FOR APPLICATIONS 2012
ADMINISTRATIVE PART
Nom de l’université: Université des Sciences Humaines et Sociales (Lille3)
Nom du président de l’université: Mr Jean-Claude DUPAS
Après avoir pris connaissance de l‟appel à candidatures « Labellisation de Sites de recherche intégrée sur le
cancer » et du présent dossier de candidature,
je soussigné, Mr Jean-Claude DUPAS,
m‟engage à soutenir et à accompagner les activités du SIRIC telles que décrites dans ce dossier de
candidature,
a pris connaissance du fait que mon établissement devra finaliser un accord de consortium avec les
partenaires et l‟établissement candidat.
Fait à Lille, le 9 décembre 2011,
Signature :
179
SIRIC - CALL FOR APPLICATIONS 2012
ADMINISTRATIVE PART
II.4. Engagement et signatures des partenaires
Nom de l’établissement partenaire : Institut de Biologie de Lille
Nom du directeur de l’établissement: Mr Yvan DE LAUNOIT
Après avoir pris connaissance de l‟appel à candidatures « Labellisation de Sites de recherche intégrée
sur le cancer » et du présent dossier de candidature,
je soussigné, Mr Yvan DE LAUNOIT,
en qualité de Directeur de l‟Institut de Biologie de Lille,
m‟engage à contribuer aux activités du SIRIC telles que décrites dans ce dossier de candidature,
a pris connaissance du fait que mon établissement devra finaliser un accord de consortium avec
les partenaires et l‟établissement candidat.
Fait à Lille, le 9 décembre 2011,
Signature :
180
SIRIC - CALL FOR APPLICATIONS 2012
ADMINISTRATIVE PART
Nom de l’établissement partenaire : CNRS délégation régionale Nord-Pas de
Calais et Picardie
Nom du directeur de l’établissement: Mme Françoise Paillous
Après avoir pris connaissance de l‟appel à candidatures « Labellisation de Sites de recherche intégrée
sur le cancer » et du présent dossier de candidature,
je soussigné, Mme Françoise Paillous,
en qualité de déléguée régionale,
m‟engage à contribuer aux activités du SIRIC telles que décrites dans ce dossier de candidature,
a pris connaissance du fait que mon établissement devra finaliser un accord de consortium avec
les partenaires et l‟établissement candidat.
Fait à Lille, le 9 décembre 2011,
Signature :
181
SIRIC - CALL FOR APPLICATIONS 2012
ADMINISTRATIVE PART
Nom de l’établissement partenaire : INSERM délégation régionale Nord-Pas de
Calais
Nom du directeur de l’établissement: Mr Samir OULD ALI
Après avoir pris connaissance de l‟appel à candidatures « Labellisation de Sites de recherche intégrée
sur le cancer » et du présent dossier de candidature,
je soussigné, Mr Samir OULD ALI,
en qualité de Délégué Régional Inserm Nord-Pas de Calais,
m‟engage à contribuer aux activités du SIRIC telles que décrites dans ce dossier de candidature,
a pris connaissance du fait que mon établissement devra finaliser un accord de consortium avec
les partenaires et l‟établissement candidat.
Fait à Lille, le 9 décembre 2011,
Signature :
182
SIRIC - CALL FOR APPLICATIONS 2012
ADMINISTRATIVE PART
Nom de l’établissement partenaire : Lille Nord de France Research and Higher
Education Cluster, PRES
Nom du directeur de l’établissement: Mr Christian SERGHERAERT
Après avoir pris connaissance de l‟appel à candidatures « Labellisation de Sites de recherche intégrée
sur le cancer » et du présent dossier de candidature,
je soussigné, Mr Christian SERGHERAERT,
en qualité de Président du PRES,
m‟engage à contribuer aux activités du SIRIC telles que décrites dans ce dossier de candidature,
a pris connaissance du fait que mon établissement devra finaliser un accord de consortium avec
les partenaires et l‟établissement candidat.
Fait à Lille, le 9 décembre 2011,
Signature :
183
SIRIC - CALL FOR APPLICATIONS 2012
ADMINISTRATIVE PART
Nom de l’établissement partenaire : Lille Cancer Research Institute
Nom du directeur de l’établissement: Mr Jean KREMBEL
Après avoir pris connaissance de l‟appel à candidatures « Labellisation de Sites de recherche intégrée
sur le cancer » et du présent dossier de candidature,
je soussigné, Mr Jean Krembel
en qualité de Directeur de l‟IRCL,
m‟engage à contribuer aux activités du SIRIC telles que décrites dans ce dossier de candidature,
a pris connaissance du fait que mon établissement devra finaliser un accord de consortium avec
les partenaires et l‟établissement candidat.
Fait à Lille, le 9 décembre 2011,
Signature :
184
SIRIC - CALL FOR APPLICATIONS 2012
ADMINISTRATIVE PART
Nom de l’établissement partenaire : Institut Pasteur de Lille
Nom du directeur de l’établissement: Mr Jacques RICHIR
Après avoir pris connaissance de l‟appel à candidatures « Labellisation de Sites de recherche intégrée
sur le cancer » et du présent dossier de candidature,
je soussigné, Mr Jacques Richir
en qualité de Directeur de l‟IPL,
m‟engage à contribuer aux activités du SIRIC telles que décrites dans ce dossier de candidature,
a pris connaissance du fait que mon établissement devra finaliser un accord de consortium avec
les partenaires et l‟établissement candidat.
Fait à Lille, le 9 décembre 2011,
Signature :
185
SIRIC - CALL FOR APPLICATIONS 2012
ADMINISTRATIVE PART
Nom de l’établissement partenaire : Lille Nord de France MESHS (European
Social sciences Centre)
Nom du directeur de l’établissement: Mme Fabienne BLAISE
Après avoir pris connaissance de l‟appel à candidatures « Labellisation de Sites de recherche intégrée
sur le cancer » et du présent dossier de candidature,
je soussigné, Mme Fabienne BLAISE
en qualité de Directrice de la MESHS,
m‟engage à contribuer aux activités du SIRIC telles que décrites dans ce dossier de candidature,
a pris connaissance du fait que mon établissement devra finaliser un accord de consortium avec
les partenaires et l‟établissement candidat.
Fait à Lille, le 9 décembre 2011,
Signature :
186
SIRIC - CALL FOR APPLICATIONS 2012
ADMINISTRATIVE PART
Nom de l’établissement partenaire : Université Catholique de Lille
Nom du directeur de l’établissement: Mme Thérèse LEBRUN
Après avoir pris connaissance de l‟appel à candidatures « Labellisation de Sites de recherche intégrée
sur le cancer » et du présent dossier de candidature,
je soussigné, Mme Thérèse Lebrun,
en qualité de Présidente,
m‟engage à contribuer aux activités du SIRIC telles que décrites dans ce dossier de candidature,
a pris connaissance du fait que mon établissement devra finaliser un accord de consortium avec
les partenaires et l‟établissement candidat.
Fait à Lille, le 9 décembre 2011,
Signature :
187
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ADMINISTRATIVE PART
Nom de l’établissement partenaire : Groupement Hospitalier de l’Institut
Catholique de Lille (University and Hospitals)
Nom du directeur de l’établissement: M. Laurent Delaby
Après avoir pris connaissance de l‟appel à candidatures « Labellisation de Sites de recherche intégrée
sur le cancer » et du présent dossier de candidature,
je soussigné, M. Laurent Delaby,
en qualité de Directeur général,
m‟engage à contribuer aux activités du SIRIC telles que décrites dans ce dossier de candidature,
a pris connaissance du fait que mon établissement devra finaliser un accord de consortium avec
les partenaires et l‟établissement candidat.
Fait à Lille, le 9 décembre 2011,
Signature :
188
SIRIC - CALL FOR APPLICATIONS 2012