LAUSR

Castrate-resistant prostate cancer (CRPC) is an incurable clinical condition that accounts for the vast majority of the >300 000 recorded deaths from this disease each year across the globe. This high level of mortality is still evident despite considerable investment in drug development over the past decade for CRPC, reflecting the intrinsic difficulty in effectively treating this disease. It may be argued that the high reliance on taxane chemotherapy and androgensignalling inhibitors as the mainstay of clinical development has been too pharmacologically narrow in focus. Recent elucidation of the genomic complexity and significant heterogeneity observed in CRPC patients [1,2] provides clear evidence that defeating this condition demands a fresh approach. In appreciating the genomic landscape of the disease, it is evident that the disease can be adequately challenged only by expanding the diversity of the cancer drug armamentarium that is used so as to target an increasingly diverse biology and one clearly wider than the preserve of the androgen signalling pathway. Exciting breakthroughs are emerging that give encouragement and optimism that such an approach has value for patients diagnosed with CRPC and the clinicians charged with their care. Profiling of CRPC tumours, for example, has identified a distinct subpopulation of disease characterised by enrichment of mutations in DNA damage-repair genes [2]. Subsequently, patients harbouring such mutations were shown to exhibit pronounced clinical responses to a poly(adenosine diphosphate–ribose) polymerase inhibitor (olaparib) in clinical trials [3]. The pursuit of further biologically informed and biomarker-guided studies will be required in each genetically defined subpopulation of CRPC so that all men afflicted by this advanced stage of disease can experience extended survival and improvements in quality of life.