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.
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.
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Published on: 17 July, 2012
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