PARP inhibitors for homologous recombination-deficient prostate cancer

ABSTRACTIntroduction: Prostate adenocarcinoma represents a leading cause of cancer-related mortality. Increased emphasis on understanding the molecular basis of prostate cancer has identified a substantial burden of homologous recombination (HR) pathway mutations, which are enriched in castrate-resistant disease. This discovery has yielded novel therapeutic opportunities.Areas covered: We will discuss the treatment of castrate-resistant prostate cancer (CRPC), with a focus on the use of poly (ADP-ribose) polymerase (PARP) inhibitors in this space. Evidence for use in HR-deficient patients will be outlined with discussion of the mechanism of action for this drug class, pathways of resistance, and approaches for expanding PARP inhibitor use to non–HR-deficient prostate cancer subgroups.Expert opinion: PARP inhibition represents an exciting tool for management of HR-inactivated CRPC. With rapid adoption of next-generation sequencing technologies and other molecular techniques, the number of patients in this ...