Ovarian cancer: Status of homologous recombination pathway as a predictor of drug response

Abstract Epithelial ovarian cancer (EOC), particularly high-grade serous subtype, is associated with germline mutations in BRCA1/BRCA2 genes in up to 20% of the patients. BRCA1/BRCA2 proteins are important components of the homologous recombination (HR) pathway, a vital DNA repair process that prote...

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Bibliographic Details
Published in:Critical reviews in oncology/hematology 2016-05, Vol.101, p.50-59
Main Authors: De Picciotto, Nicolas, Cacheux, Wulfran, Roth, Arnaud, Chappuis, Pierre O, Labidi-Galy, S. Intidhar
Format: Article
Language:English
Subjects:
Alkylating agents
Animals
Antineoplastic Agents - therapeutic use
BRCA mutation
BRCA1 Protein - genetics
BRCA2 Protein - genetics
BRCAness
Female
Germ-Line Mutation
Hematology, Oncology and Palliative Medicine
Homologous Recombination
HRness
Humans
Ovarian cancer
Ovarian Neoplasms - drug therapy
PARP inhibitor
Platinum
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Summary:Abstract Epithelial ovarian cancer (EOC), particularly high-grade serous subtype, is associated with germline mutations in BRCA1/BRCA2 genes in up to 20% of the patients. BRCA1/BRCA2 proteins are important components of the homologous recombination (HR) pathway, a vital DNA repair process that protects the genome from double-strand DNA damage. Recent studies revealed frequent somatic mutations of BRCA1/BRCA2 and hypermethylation of the promoter of BRCA1 in EOC, in addition to germline mutations. Comparison of DNA copy number changes in tumors with or without BRCA1/BRCA2 alterations, lead to the identification of several signatures that detect HR pathway defects, here named “HRness”. These signatures predict platinum-sensitivity and survival in EOC, as it was previously shown for germline mutations of BRCA1/BRCA2 . They are currently investigated in clinical trials as potential predictive biomarker for response to poly(ADP- ribose) polymerase inhibitors.
ISSN:1040-8428
1879-0461
DOI:10.1016/j.critrevonc.2016.02.014