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

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• 作者：Nicolas De Picciotto^aAuthor Vitae ; Wulfran Cacheux^a ; Arnaud Roth^a ; Pierre O. Chappuis^a ; ^b ; S. Intidhar Labidi-Galy^a ; ^{intidhar.labidi-galy@hcuge.ch" class="auth_mail" title="E-mail the corresponding author}Author Vitae
• 关键词：Ovarian cancer ; BRCAness ; Homologous recombination ; Platinum ; PARP inhibitor ; Alkylating agents ; HRness ; BRCA mutation
• 刊名：Critical Reviews in Oncology and Hematology
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：101
• 期：Complete
• 页码：50-59
• 全文大小：1215 K

文摘

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.