Oncotarget

Reviews:

BRCA mutations in the manifestation and treatment of ovarian cancer

Zimin Pan and Xing Xie _

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Oncotarget. 2017; 8:97657-97670. https://doi.org/10.18632/oncotarget.18280

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Abstract

Zimin Pan1 and Xing Xie1

1 Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China

Correspondence to:

Xing Xie, email: xie.xing@yahoo.com

Keywords: BRCA, ovarian cancer, pathogenesis, chemotherapy, targeted therapy

Received: February 14, 2017     Accepted: April 28, 2017     Published: May 30, 2017

ABSTRACT

BRCA genes are important for the integrity and stability of genetic material and play key roles in repairing DNA breaks via high fidelity homologous recombination. BRCA mutations are known to predispose carriers to gynecological malignancies, accounting for a majority of hereditary OC cases. Known to be lethal, OC is difficult to detect and control. Testing for BRCA mutations is a key step in the risk assessment, prognosis, treatment and prevention of OC and current clinical guidelines recommend BRCA mutation testing for all OCs of epithelial origin. Studies have established that ovarian tumors harboring BRCA mutations have distinct molecular and histo-pathological features that can be exploited for effective, targeted treatment. Deficiencies in DNA repair pathways that arise as a result of BRCA mutations make them hypersensitive to DNA-damaging treatments such as platinum chemotherapy and PARP inhibitors. Different combinations of treatment regimens which have the potential to greatly improve prognosis and disease outcomes are currently being evaluated. However, the issue of developing resistance to these treatments remains unresolved. This review emphasizes unique features of BRCA mutated OC and outlines the lay of the land in terms of diagnosis and treatment, while aiming to unravel the challenges that are part of its management.


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