The circuitous path of PARP inhibitor development in epithelial ovarian cancer.

摘要

Ovarian cancers account for more than 50% of gynecologic cancer deaths. This is attributable to the late stage of the disease at diagnosis. Overall, 22,280 new cases of epithelial ovarian cancer and 15,500 deaths are estimated for 2012. [1] Although ovarian cancer is highly sensitive to initial platinum-based chemotherapy, with response rates of 70% to 90% in previously untreated patients, only 30% are cured by upfront surgery and chemotherapy. [2,3] The remaining cases will relapse, and cure after relapse is unlikely. Rational therapies directed toward specific molecular targets, and a better understanding of the mechanisms of action and resistance of novel agents, are urgently needed to improve survival of patients with recurrent ovarian carcinoma. Recently, PARP inhibitors, which impair the base excision DNA repair (BER) pathway, have been emerging as promising targeted therapies.