Download Dr Colin Watts, Cambridge University

Opportunities for Addressing
Unmet Clinical Need in Brain
Cancer
Colin Watts
[email protected]
Brain Cancer has a disproportionate burden of
disease on the individual that is poorly
recognised
• Brain Cancer accounts
for 2% of cancers but
7% of cancer deaths
• Astrocytic tumours
are the third leading
cause of cancer
related death in
middle aged men
• Astrocytic tumours
are the fourth leading
cause of death among
women aged 15-34
Glioblastoma is biologically complex at
presentation
Biological Timeline
Surgery'
Radiotherapy'
Concomitant'
Chemotherapy'
Clinical
Presenta on
Adjuvant'Chemotherapy'
Pallia%ve(Surgery(
Clinical Progression
Clinical Timeline
Pallia%ve(Chemotherapy(
Pa ent Death
So how can we develop multimodal
precision therapeutics?
We can interrogate spatial and temporal intratumour
heterogeneity in patients in real time to establish a
biological rationale for drug targeting
A
C
T1
T2
T3
B
B
C
T4
We can develop a patient-derived xenogeneic
platform for high-throughput screening &
technology development
Brain tumour tissue
dissociation and cell
plating in EGF-bFGF
containing medium
Proliferation
Dissociation and
Primary spheres plating in EGF-bFGF
containing medium
Differentiation
and/or cell
death
Removal of EGF
and bFGF
Proliferation
Triple labelling
immunostaining
Removal of EGF
and bFGF
Secondary spheres
Differentiation
Dissociation and
plating in EGF-bFGF
containing medium
Removal of EGF
and bFGF
Tertiary spheres
Differentiation
Proliferation
Differentiation
and/or cell
death
An example of multimodal
therapeutics through
nanotechnology
Setua et al 2014 Nanoscale 6 (18)
10685-73
Aim of the project
 Development of peptide functionalized drug-gold nanoparticle
conjugate for targeted chemoradiotherapy of GBM
(We use patient derived GBM cells)
(MUA)
AuNP: Gold nanoparticle
Radiosensitizing potential of AuNP
Control + RT
AuNP-HSA + RT
AuNP-PEI + RT
Growth Curve : GBM cell line
GBM xenograft model
P = 0.0486
Control
Control + RT
AuNP-PEI
AuNP-PEI + RT
* = P < 0.05, ** = P < 0.01, *** = P < 0.001
 AuNP + RT can not decrease the growth of GBM cells effectively.
Radiosensitizing potential of AuNP-Pt
Control+RT
AuNP-MUA+ RT
AuNP-Pt + RT
* = P < 0.05
*** = P < 0.001
 AuNP-Pt + RT can decrease the growth of GBM cells significantly.
What do we need?
• Targeted delivery specifically to tumour
cells
• Capacity to deliver multiple drug payloads
• Maximise therapeutic efficacy
• Minimise toxicity associated with combinatorial
therapeutics
• Local and systemic therapies
• Real-time diagnostics that can control for
biological heterogeneity
How can we do this?
• Strategies for tumour-cell targeting
• Linking biology & technology
• Developing a (nano)technology platform
• High-throughput evaluation using validated
biological platforms
• In silico modelling
• Tunable adaptive technology to deliver precison
therapeutics
[email protected]