Routes to prostate cancer progression and identification of new drug targets: results from the CRUK-ICGC prostate initiative


Year:

Session type:

Rosalind Eeles1,David Wedge2,Gunes Gundem2,Thomas Mitchell2,Mohammed Ghori2,Adam Butler2,Hayley Whitaker3,Zsofia Kote-Jarai1,Charlie Massie4,Ludmil B. Alexandrov3,Anne Y. Warren5,Clare Verrill6,Dan Berney7,Nening Dennis1,Susan Merson1,Chris Sander8,Freddie C. Hamdy9,Ultan McDermott2,Bissan Al-Lazikani1,Paul Workman1,Andy G. Lynch3,G. Steven Bova10,Christopher S. Foster11,Daniel S. Brewer12,David Neal2,Colin Cooper12
1The Institute of Cancer Research,2Wellcome Trust Sanger Institute,3Cancer Research UK, Cambridge Institute,4University of Cambridge,5Cambridge University Hospitals NHS Foundation Trust,6Oxford University,7Barts Cancer Centre, Barts and the London School of Medicine & Dentistry,8Dana Farber Cancer Institute & Harvard Medical School,9University of Oxford,10University of Tampere, BioMediTech,11HCA Healthcare,12The University of East Anglia

Abstract

Background

Prostate cancer (PCa) is a challenge to treat because, while some cases are indolent, others progress and cause morbidity and mortality.

Method

We sequenced the whole genomes of 112 primary and metastatic PCas to 50X and their associated germline DNA to 30X through the CRUK - ICGC prostate cancer project. We then combined these data with publically available sequence data from prostate cancers in the TCGA.

Results

We identified 18 novel putative driver genes. Through the temporal dissection of aberrations and the stratification of tumours by ETS status and primary/metastatic site, we identified driver mutations specifically associated with steps in the progression of PCa.

Conclusion

Using the CanSAR analysis of mutations which is a bioinformatic tool to predict which products may be susceptible to current drug targets, we identified 8 targets of current drugs, 6 targets of investigational drugs and 26 compounds that may be active and should be considered as trial candidates in future clinical trial design in this disease.