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Tailoring Ovarian Cancer Treatment: Implications of BRCA1/2 Mutations.


ABSTRACT: High grade serous ovarian cancer (HGSOC) is the most common epithelial ovarian cancer, harbouring more than 20% germline or somatic mutations in the tumour suppressor genes BRCA1 and BRCA2. These genes are involved in both DNA damage repair process via homologous recombination (HR) and transcriptional regulation. BRCA mutation confers distinct characteristics, including an increased response to DNA-damaging agents, such us platinum chemotherapy and poly-ADP ribose polymerase inhibitors (PARPi). However, several mechanisms of resistance to these agents have been described, including increased HR capacity through reverse BRCA mutations, non-homologous end-joint (NHEJ) repair alterations and drug efflux pumps. Current treatments of ovarian cancer including surgery, chemotherapy, targeted treatment and maintenance strategies, as well as resistance mechanisms will be reviewed, focusing on future trends with respect to BRCA mutation carriers.

SUBMITTER: Madariaga A 

PROVIDER: S-EPMC6468364 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Tailoring Ovarian Cancer Treatment: Implications of <i>BRCA1/2</i> Mutations.

Madariaga Ainhoa A   Lheureux Stephanie S   Oza Amit M AM  

Cancers 20190323 3


High grade serous ovarian cancer (HGSOC) is the most common epithelial ovarian cancer, harbouring more than 20% germline or somatic mutations in the tumour suppressor genes <i>BRCA1</i> and <i>BRCA2</i>. These genes are involved in both DNA damage repair process via homologous recombination (HR) and transcriptional regulation. <i>BRCA</i> mutation confers distinct characteristics, including an increased response to DNA-damaging agents, such us platinum chemotherapy and poly-ADP ribose polymerase  ...[more]

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