Development of PARP Inhibitors for BRCA-Deficient Epithelial Ovarian Cancer

Recent trials of the poly(ADP-ribose) polymerase (PARP) inhibitors olaparib, rucaparib and niraparib have resulted in approval of these agents in ovarian cancer, initially in patients with germline BRCA1 or BRCA2 mutations, now extended to the maintenance setting for all platinum-sensitive ovarian cancer. PARP inhibitors were first developed as chemo-sensitising agents and early clinical trials focused on combination treatment with DNA-damaging chemotherapy. However, the identification of synthetic lethality of PARP inhibitor treatment in BRCA1 and BRCA2-mutant cancer led to trials in BRCA1/2-mutant ovarian cancer with clinical responses to single agent treatment. These DNA-repair targeted agents have been a success story of translational research. However, questions remain over their optimal use in ovarian cancer and the effectiveness of currently available predictive biomarkers.