Download Dr Angela Kukula, Director of Enterprise, Institute of Cancer Research

Promoting Excellence in UK
Cancer Research
Dr Angela Kukula
The Institute of Cancer Research, London
Outline
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Recent advances in cancer research
and treatment
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Translating research into patient
impact
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Accommodating future advances
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Research Excellence and Impact
• Ranked first in the Times Higher Education league table of university
research quality – based on peer reviewed Research Excellence Framework
(REF 2014)
• Top for both excellence and impact
• We came joint top of academic research institutions worldwide in the Times
Higher Education/ Elsevier table for Innovation – based on the proportion of
our research papers cited in patents
• We were awarded the UK’s only Regius Professorship of Cancer Research
by the Queen in 2016
• Together with The Royal Marsden we are rated in the top four Cancer
Centres globally measured by citation impact (Thomson Reuters)
• We have identified 20 potential new cancer drugs since 2005, with 9 entering
clinical trials and 1, abiraterone, approved.
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Recent advances in cancer research
and treatment
Extraordinary advances in
understanding cancer biology
Hallmark traits of cancer
Hanahan & Weinberg Cell 100 57-70 2000
Cancer genes & pathways
Vogelstein et al 339 1546-58 2013
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Cancer gene sequencing
Identifying and
targeting individual
patient mutations
both in the original
tumour and
throughout therapy
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Circulating DNA and tumour cells
• Circulating tumour cells (CTCs) are
cells that have shed into the blood
stream or lymphatic system from a
primary tumour and are carried
around the body in the circulation
• Numbers are very small
• Capture and characterisation allows
monitoring of tumour treatment,
evolution and development of
resistance in real time
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Precision Medicine
Drugging hallmark traits
We have seen some exciting
new targeted therapies
developed for cancer.
Each new targeted drug
teaches us more about how
cancers develop and
respond to treatment, and
increases the chances of
creating better drugs or
treatment combinations.
Hanahan & Weinberg Cell 144 646-674 2011
Immuno-oncology
• Over 100 years old – Coley toxins
• Monoclonal antibodies
• Transtuzumab (Herceptin)
• Immune checkpoints
• PD1 receptor inhibitors (Keytruda)
• Conjugated antibodies
• Ado-trastuzumab emtansine (Kadcyla)
• Vaccines
• Preventative – HPV
• Treatment – sipuleucel T (Provenge)
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Immuno-oncology
• CAR T cells
Dramatic results in
haematological
cancers
Recent evidence of
utility in solid tumours
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Radiotherapy developments
START trials
The START trials looked at radiotherapy dose schedules in women with
early-stage breast cancer.
Using fewer, larger fractions gave
comparable levels of cancer control.
The study has had widespread impact on
international clinical practice.
In the UK, we are now using 250,000 fewer
fractions of radiotherapy each year, saving
the NHS £50 million per year.
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Radiotherapy developments
MR-Linac
• Technical radiation development will increase cure
rates of curable cancers and reduce toxicities.
• MR-Linac – a game changer that will also open up new
indications in tumours that have been traditionally
regarded as off limits.
• Software solutions to RT planning and RT delivery will
significantly improve our ability to treat curable cancers.
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Analysis of pan-cancer sequence data
Workman & Al-Lazikani Nat Rev Drug Discov 12 889-90 2013
Large-scale omics
• Hypothesis-driven
• Functional screens
Identifying cancer driver genes
Frequency
‘Mountains’
• Non-oncogene addiction
Objective assessment of cancer drivers
58 persistent
drivers
Genes
8 Drug targets
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With drug-like
bioactive
compounds
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No current
evidence for
druggability
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58
10
385
513
• Network biology
127 TCGA
pan-cancer drivers
11 Drug targets
High
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With drug-like
bioactive
compounds
14 Druggable
8 Druggable
Alternative
studies
• Synthetic lethality
‘Hills’
Evidence for target being actionable
Genome
sequencing
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No current
evidence for
druggability
TCGA
pancancer
Drug discovery
and development
Personalized
cancer therapy
Low
Diagnostic and
prognostic biomarkers
Patient stratification
Challenges we still need to overcome
in cancer treatment
• Many targeted cancer drugs are effective
initially, only for drug resistance to develop
• Tumours are extremely genetically diverse, and
can evolve dynamically over time – survival of
the nastiest
• Tumour evolution is forcing us to develop new
approaches to treatment to ensure we stay
ahead of drug resistance
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Overcoming this challenge
Innovation in cancer treatments
• Using targeted drugs in combination or with other
treatments including radiotherapy and
immunotherapies
• Network drugs tackle more than one cellular
signaling pathway and hit cancer harder
• Circulating tumour cells and DNA allows us to
monitor genetic changes within patients over the
course of their treatment.
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Earlier detection
• Alongside innovation in treatment we also need
innovation in detection technologies
•Both detection of the primary tumour and detection
of developing resistance or metastases
•Every cancer is curable – if we find it soon enough.
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Innovation in science and medicine
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Translating research into patient
impact
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Our partnership with The Royal
Marsden
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ICR’s partnership with The Royal Marsden
forms one of the largest comprehensive
cancer centres in Europe
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Spanning basic cancer research to practicechanging trials and specialist healthcare
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Facilitates our rapid ‘bench-to-bedside and
back’ approach
Together we are rated in the top
four comprehensive cancer
centres worldwide for impact on
cancer research and treatment
– Thomson Reuters
Making the discoveries
Our strategy to defeat cancer
The ICR and The Royal Marsden
have worked together on a joint
strategy covering the next five years.
Our vision
We will overcome the challenges
posed by cancer’s complexity,
adaptability and evolution through
scientific and clinical excellence,
innovation and partnership.
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Making the discoveries
The four pillars of our strategy
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Unravelling cancer’s complexity
We will comprehend the full complexity of cancer by harnessing the
power of new technologies and Big data.
Innovative approaches
We will take on the challenge of cancer’s complexity, evolution and
drug resistance through the discovery of innovative new
approaches to cancer treatment.
Smarter, kinder treatments
We will move a step closer to cure by bringing personalised
treatments into the clinic and developing them for patients.
Making it count
We will deliver better outcomes and improved quality of life for
patients by establishing innovative treatments, diagnostics and
strategies for prevention as part of routine healthcare.
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Working in partnership
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Working in
partnership both with
other academic
institutions and with
industry is positively
encouraged
It is essential to bring
together
complimentary skills
and expertise to
allow us to bring our
discoveries to
patients faster
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The London Cancer Hub
A global centre for cancer innovation
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The London Cancer Hub aims to
create a world-leading
life-science campus specialising in
cancer research, healthcare,
education and biotech innovation.
We will provide state-of-the-art facilities,
and be joined by a series of high-tech
enterprises in a network of 10,000
researchers, clinical staff and support
staff all operating from one site.
We plan to deliver an exceptional
environment for cancer research
that enhances the discovery of new
treatments and their development
for patients
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Innovation in science and medicine
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Is innovation currently affordable?
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Accommodating future advances
Why are the costs of innovation so
high?
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• Targeted treatments work in smaller patient populations than
the blockbusters of the past. The risks remain high while the
potential returns are lower.
• The drugs coming through are just too expensive for health
care systems. Innovation is coming to be seen as unaffordable.
• This in turn acts as a disincentive for drug companies to
innovate in small populations.
• We need to reduce costs by approving and running smaller,
smarter, more stratified trials – and passing the costs savings
down the line.
Approvals for innovative trials
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Willingness of the
pharmaceutical industry to
embrace new trials designs
Risk sharing approaches
that make it easier for
companies to take risks
A price system that is
affordable and
incentivises innovation
A regulatory system which allows
innovative approaches and early
adoption of new medicines
Evaluation systems
which recognise
innovation
Combination treatments
• Using rational combinations of drugs against same or several
pathways at once has the potential to address tumour
heterogeneity and evolution
• But use of combinations poses challenges in:
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trial design
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approvals
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“real time” combination prescribing
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price
If we are to see improvements in survival and cure rates we
need to improve the affordability and accessibility of combination
therapies.
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Drug pricing
We need to build confidence that health systems will pay for the most
innovative and effective cancer treatments.
Innovation needs to be embedded
throughout the whole process of
bringing a drug to market, including
at the drug approval and cost
evaluation stage.
We need innovative ways of pricing
combination therapies
As regulators increasingly approve
drugs based on phase 2 data we
need pricing models that can accept
this immature overall survival data
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Scientific opportunities for innovation
• Basic, translational and clinical research are all
important in understanding cancer and improving
treatments.
• Research looking more comprehensively at cancer on a
network or systems level is increasingly becoming
important.
• Major breakthroughs in understanding cancer will
continue and we will overcome clonal evolution and drug
resistance – and find ways to stay ahead of cancer.
•But we must find ways to ensure that these innovations
are available to health care providers at an affordable
price.
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