Toggle Main Menu Toggle Search

Open Access padlockePrints

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 Curtin, Professor Richard Edmondson

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

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

URL: http://dx.doi.org/10.1158/0008-5472.CAN-12-0324

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


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share