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Clinicopathological Features of Homologous Recombination-Deficient Epithelial Ovarian Cancers: Sensitivity to PARP Inhibitors, Platinum, and Survival

Lookup NU author(s): Dr Asima Mukhopadhyay, Professor Ruth Plummer, Dr Ahmed Elattar, Dr San Soo Hoo, Bisha Uzir, Professor Nicola CurtinORCiD, Professor Richard Edmondson


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Up to 50% of epithelial ovarian cancers (EOC) display defects in the homologous recombination (HR) pathway. We sought to determine the ramifications of the homologous recombination-deficient (HRD) status on the clinicopathologic features, chemotherapy response, and survival outcomes of patients with EOCs. HR status was determined in primary cultures from ascitic fluid in 50 chemotherapy-naive patients by a functional RAD51 immunofluorescence assay and correlated with in vitro sensitivity to the PARP inhibitor (PARPi), rucaparib. All patients went on to receive platinum-based chemotherapy; platinum sensitivity, tumor progression, and overall survival were compared prospectively in HR-competent versus HRD patients. Compared with HR-competent patients, the HRD group was predominantly serous with a higher median CA125 at presentation. HRD was associated with higher ex vivo PARPi sensitivity and clinical platinum sensitivity. Median follow-up duration was 14 months; patients in the HRD group had lower tumor progression rates at 6 months, lower overall/disease-specific death rates at 12 months, and higher median survival. We therefore suggest that HRD as predicted by a functional RAD51 assay correlates with in vitro PARPi sensitivity, clinical platinum sensitivity, and improved survival outcome. Cancer Res; 72(22); 5675-82. (C) 2012 AACR.

Publication metadata

Author(s): Elattar A; Mukhopadhyay A; Uzir B; Plummer ER; Curtin NJ; Edmondson RJ; Soohoo S; Quinn JE; McCluggage WG; Maxwell P; Aneke H

Publication type: Article

Publication status: Published

Journal: Cancer Research

Year: 2012

Volume: 72

Issue: 22

Pages: 5675-5682

Print publication date: 11/10/2012

ISSN (print): 0008-5472

ISSN (electronic): 1538-7445

Publisher: American Association for Cancer Research


DOI: 10.1158/0008-5472.CAN-12-0324


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