The Role of PARP Inhibitors in the Treatment of Ovarian Carcinomas

Title:The Role of PARP Inhibitors in the Treatment of Ovarian Carcinomas

Volume: 18 Issue: 25

Author(s): Anna V. Tinker and Karen Gelmon

Affiliation:

Keywords: Ovarian carcinoma, PARP inhibitors, high grade serous carcinomas, BRCA1 and BRCA2, Homologous recombination (HR), DNA double strand break (DSB) repair, single strand DNA breaks (SSB), synthetic lethality, mutation carriers, clinical data.

Abstract: Homologous recombination (HR), a key mechanism of DNA double strand break (DSB) repair, is commonly defective in high grade serous carcinomas (HGSC) of the ovary. BRCA1/2 mutations, as well as many other molecular and genetic defects, can lead to impaired HR. Treatment of HR-defective tumours with poly-ADP ribose polymerase (PARP) inhibitors, which block the key mechanism of single strand DNA breaks (SSB), exploits a therapeutic concept called “synthetic lethality”. Early experiences with PARP inhibitors in germline BRCA mutation carriers and sporadic HGSCs of the ovary have been promising. The development of PARP inhibitors for ovarian cancer is an area of active research. This article provides an overview of the molecular rationale for the use of PARP inhibitors and summarizes some of the key early clinical data of their use in ovarian cancer.

Cite this article as:

V. Tinker Anna and Gelmon Karen, The Role of PARP Inhibitors in the Treatment of Ovarian Carcinomas, Current Pharmaceutical Design 2012; 18 (25) . https://dx.doi.org/10.2174/138161212802002823