: High-grade serous ovarian cancer is characterized by genomic instability, with 
one half of all tumors displaying defects in the important DNA repair pathway of 
homologous recombination. Given the action of poly(ADP-ribose) polymerase (PARP) 
inhibitors in targeting tumors with deficiencies in this repair pathway by loss 
of BRCA1/2, ovarian tumors could be an attractive population for clinical 
application of this therapy. PARP inhibitors have moved into clinical practice 
in the past few years, with approval from the Food and Drug Administration (FDA) 
and European Medicines Agency (EMA) within the past 2 years. The U.S. FDA 
approval of olaparib applies to fourth line treatment in germline BRCA-mutant 
ovarian cancer, and European EMA approval to olaparib maintenance in both 
germline and somatic BRCA-mutant platinum-sensitive ovarian cancer. In order to 
widen the ovarian cancer patient population that would benefit from PARP 
inhibitors, predictive biomarkers based on a clear understanding of the 
mechanism of action are required. Additionally, a better understanding of the 
toxicity profile is needed if PARP inhibitors are to be used in the curative, 
rather than the palliative, setting. We reviewed the development of PARP 
inhibitors in phase I-III clinical trials, including combination trials of PARP 
inhibitors and chemotherapy/antiangiogenics, the approval for these agents, the 
mechanisms of resistance, and the outstanding issues, including the development 
of biomarkers and the rate of long-term hematologic toxicities with these 
agents.
IMPLICATIONS FOR PRACTICE: The poly(ADP-ribose) polymerase (PARP) inhibitor 
olaparib has recently received approval from the Food and Drug Administration 
(FDA) and European Medicines Agency (EMA), with a second agent (rucaparib) 
likely to be approved in the near future. However, the patient population with 
potential benefit from PARP inhibitors is likely wider than that of germline 
BRCA mutation-associated disease, and biomarkers are in development to enable 
the selection of patients with the potential for clinical benefit from these 
agents. Questions remain regarding the toxicities of PARP inhibitors, limiting 
the use of these agents in the prophylactic or adjuvant setting until more 
information is available. The indications for olaparib as indicated by the FDA 
and EMA are reviewed.