Distinct implications of different BRCA mutations: efficacy of cytotoxic chemotherapy, PARP inhibition and clinical outcome in ovarian cancer

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Abstract

Approximately a fifth of ovarian carcinoma (OC) is associated with inherited germline mutations, most commonly in the DNA repair genes BRCA1 or BRCA2 (BRCA). BRCA1- and BRCA2-associated OCs have historically been described as a single subgroup of OC that displays a distinct set of characteristics termed the "BRCAness" phenotype. The hallmarks of this phenotype are superior clinical outcome and hypersensitivity to platinum-based chemotherapy and poly-(ADP-ribose) polymerase (PARP) inhibitors. However, growing evidence suggests that BRCA1- and BRCA2-associated OCs display distinct characteristics, most notably in long-term patient survival. Furthermore, recent data indicate that the site of BRCA1 mutation is important with regard to platinum and PARP inhibitor sensitivity. Here, we summarize the body of research describing the BRCAness phenotype and highlight the differential implications of different BRCA mutations with regard to clinicopathologic features, therapy sensitivity and clinical outcome in OC.

Original languageEnglish
Pages (from-to)2539-2551
Number of pages13
JournalOncoTargets and Therapy
Volume10
DOIs
Publication statusPublished - 11 May 2017

Keywords

  • ovarian cancer
  • BRCA1
  • BRCA2
  • BRCAness

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