Targeting homologous repair deficiency in breast and ovarian cancers: Biological pathways, preclinical and clinical data

Published on Jan 1, 2019in Critical Reviews in Oncology Hematology5.01
· DOI :10.1016/j.critrevonc.2018.10.012
Elodie Chartron1
Estimated H-index: 1
Charles Theillet56
Estimated H-index: 56
(University of Montpellier)
+ 1 AuthorsWilliam Jacot25
Estimated H-index: 25
(University of Montpellier)
Abstract Mutation or epigenetic silencing of homologous recombination (HR) repair genes is characteristic of a growing proportion of triple-negative breast cancers (TNBCs) and high-grade serous ovarian carcinomas. Defects in HR lead to genome instability, allowing cells to acquire the multiple genetic alterations essential for cancer development. However, this deficiency can also be exploited by using DNA damaging agents or by targeting compensatory repair pathways. A noteworthy example is treatment of TNBC and epithelial ovarian cancer harboring BRCA1/2 germline mutations using platinum salts and/or PARP inhibitors. Dramatic responses to PARP inhibitors may support a wider use in the HR-deficient population beyond those with mutated germline BRCA1 and 2. In this review, we discuss HR deficiency hallmarks as predictive biomarkers for platinum salt and PARP inhibitor sensitivity for selecting patients affected by TNBC or epithelial ovarian cancer who could benefit from these therapeutic options.
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