Journal
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
Volume 133, Issue -, Pages 58-73Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.critrevonc.2018.10.012
Keywords
Triple-negative breast cancer; Epithelial ovarian cancer; Homologous recombination deficiency; BRCAness; Prognostic biomarker; Predictive biomarker; Platinum salts; PARP inhibitor
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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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