1. NISCHR Academic Health Science Collaboration Launch
NISCHR Academic Health Science Collaboration Launch
Millennium Stadium
Cardiff
3 March 2011 1

2. Cancer Research in Partnership: Selection and Stratification
Cancer Research in Partnership: Selection and Stratification
Professor Malcolm Mason,
Head of Oncology & Palliative Medicine,
Cardiff University

3. We are not all the same

4. Are cancers all the same??
Gleevec in CML
Gefitinib in lung cancer
Cetuximab in colorectal cancer

5. The EGFR pathway

6. The Gleevec story: CML
Specific gene fusion product BCR-ABL from t9:22 gene translocation
Gleevec blocks specific molecular driver of disease
Also active in GIST

7. The Gleevec story: CML

8. The Gefitinib story A new treatment for lung cancer
Binds to ATP-binding site of EGFR
Can’t fail......

9. The Gefitinib story
WHY???????

10. Predictors of response to Gefitinib in lung cancer?
Adenocarcinoma
EGF mutations
Non-smokers
Asian patients

11. West Japanese Oncology Group study in adenocarcinoma of the lung

12. Cetuximab in colorectal cancer - predictive factors

13. The message: Cancers are all different Certain molecular subtypes respond to certain treatments

14. Variants at every level
Predisposition genes and cancer risk
Biological variation in aggressiveness
Genetic and other biological determinants of response to treatment
Tumour (expressing a drug target)
Host (how drugs are handled)

15. How do we unravel all this?
GWAS studies: extensive, very large, undertaken in several common cancer types
e.g. colorectal cancer, approx 7,000 cases and 7,000 controls from worldwide study
Post-GWAS: what does it all mean?
Functional studies in human tumours
Very large numbers needed!

16. If a gene increases the risk of cancer by 10-20% (odds ratio 1.1-1.2)
For 90% power
57,000 samples required
& Prof Ros Eeles, personal communication

17. This needs parntership
NHS
Universities
Industry
Patients & relatives

18. Wales Cancer Bank
Collection of tumour and blood from patients at 7 hospitals in Wales
To date 4,600 patients consented
Linked-anonymised to Canisc for clinical and outcome data

19. Wales Cancer Bank Molecular characterisation of the tissues we hold
Colorectal (k-ras, B-raf, PTEN)
Prostate (TMPRSS2-ERG, PTEN)
Breast (PI3CKA, p53, PTEN, YP2D6)
Link biological and clinical data

20. The new NISCHR BRU in Cancer
Cardiff University
School of Medicine
School of Biosciences
Bangor University

21. The new NISCHR BRU in Cancer
Predisposition genes and pharmacogenomics(colorectal cancer)
Molecular prognostic factors in leukaemia
Transfer of other models (yeast and mouse models) to human cancers
Assessing DNA repair in human cells
Bioinformatics

22. Clinical Research Smarter clinical trials:
Combined RT and EGFR blockade
Advanced imaging (PET)
Lung cancer and mesothelioma
Palliative care
Defining the prevalence and role of HPV in head and neck cancers
Enhanced collection of tumour samples (lung cancer)