BRCA mutations in the manifestation and treatment of ovarian cancer.

Zimin Pan,Xing Xie

doi:10.18632/oncotarget.18280

Zimin Pan, Xing Xie

Open Access

https://doi.org/10.18632/oncotarget.18280

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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.

Highlights

Ovarian cancer (OC) is known to cause the largest number of deaths among cancers of gynecologic origin
The results showed a better progression-free survival (PFS) in BRCA mutation positive patients treated with platinum based chemotherapy administered via the IP route, with a clinically insignificant effect on overall survival (OS) [72]
Primarily of epithelial origin, is one of the major tumor types that is associated with BRCA mutations

Summary

Introduction

Ovarian cancer (OC) is known to cause the largest number of deaths among cancers of gynecologic origin. Autosomally transmitted hereditary OC arises from mutations in 2 key types of genes: the BRCA (breast cancer susceptibility) genes (called hereditary breast and OC [HBOC] syndrome) and the MMR (DNA mismatch repair) genes (called hereditary non-polyposis colorectal cancer [HNPCC] syndrome or Lynch II syndrome) [1]. Both sets of genes are involved in the repair of genetic lesions. The BRCA genes are tumor suppressors, and a mutation in either one is known to predispose carriers to several types of cancer [4, 5]

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