BACKGROUND: Slow progress in improving the outcome of ovarian cancer with 
chemotherapy over the last decade has stimulated research into molecularly 
targeted therapy. Poly(ADP-ribose) polymerase (PARP) inhibitors target DNA 
repair and are specifically active in cells that have impaired repair of DNA by 
the homologous recombination (HR) pathway. Cells with mutated BRCA function have 
HR deficiency (HRD), which is also present in a significant proportion of 
non-BRCA-mutated ovarian cancer.
DESIGN: In the last decade, olaparib, the first and most-investigated oral PARP 
inhibitor, has undergone phase I-III trials as a single agent, in comparison 
with and in addition to chemotherapy, and as a maintenance therapy following 
chemotherapy.
RESULTS: The greatest benefit to-date has been in the maintenance setting, 
prolonging the progression-free survival of high-grade serous ovarian cancer 
with a BRCA1/2 mutation. In this group of patients, olaparib has received 
approval as maintenance following chemotherapy from the EMA, and accelerated 
approval as a single agent in women who have had three or more lines of therapy. 
Olaparib can be given for a prolonged period with few significant side-effects 
in most patients. Similar trials with other PARP inhibitors (rucaparib, 
niraparib and veliparib) are in progress and include non-BRCA-mutated ovarian 
cancer. Second-generation studies are exploring the combination of PARP 
inhibitors with anti-angiogenic drugs.
CONCLUSIONS: PARP inhibitors represent a step change in the management of 
ovarian cancer. BRCA mutations are the first genotypic predictive markers in 
ovarian cancer and can be used to select patients who will most likely benefit 
from PARP inhibitors. BRCA testing is now becoming a routine part of the 
evaluation of women with ovarian cancer, and tests for HRD are being used to 
evaluate PARP inhibitors in an extended population of non-BRCA-mutated ovarian 
cancer.