Evaluation of DNA Repair Function as a Predictor of Response in a Clinical Trial of PARP Inhibitor Monotherapy for Recurrent Ovarian Carcinoma.

Ovarian cancer is the fifth leading cause of cancer death among American women. Identifying personalized drugs that can target individual defects in cancers could improve response to therapy and decrease toxicity. PARP inhibitors are anti-cancer drugs that work best in cancers that don't repair damaged DNA well. We propose to apply modern sequencing and molecular technologies to assess DNA repair function in ovarian cancers from women treated in a prospective clinical trial of the PARP inhibitor rucaparib. We will see if our sequencing test can predict which cancers will respond to the PARP inhibitor. Such a predictive test will facilitate the rational and cost-effective application of PARP inhibitors in the therapy of sporadic ovarian carcinoma. It is likely that predictive tests or 'biomarkers' developed from this trial would also be applicable in hereditary as well as sporadic ovarian carcinoma and might also be applicable to other cancer types. We hope our data will allow more women with ovarian carcinoma to benefit from treatment with a PARP inhibitor and encourage companies to expand the use of these drugs to those cancer patients who are most likely to benefit.