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Ovarian Cancer Therapy: Homologous Recombination Deficiency as a Predictive Biomarker of Response to PARP Inhibitors

Miller, Rowan E; Elyashiv, Osnat; El-Shakankery, Karim H; Ledermann, Jonathan A; (2022) Ovarian Cancer Therapy: Homologous Recombination Deficiency as a Predictive Biomarker of Response to PARP Inhibitors. OncoTargets and Therapy , 15 pp. 1105-1117. 10.2147/ott.s272199. Green open access

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Abstract

Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have revolutionised the management of patients with high-grade serous and endometrioid ovarian cancer demonstrating significant improvements in progression-free survival. Whilst the greatest benefit is seen with BRCA1/2 mutant cancers, it is clear that the benefit extends beyond this group. This sensitivity is thought to be due to homologous recombination deficiency (HRD), which is present in up to 50% of the high-grade serous cancers. Several different HRD assays exist, which fall into one of three main categories: homologous recombination repair (HRR)-related gene analysis, genomic “scars” and/or mutational signatures, and real-time HRD functional assessment. We review the emerging data on HRD as a predictive biomarker for PARP inhibitors and discuss the merits and disadvantages of different HRD assays.

Type: Article
Title: Ovarian Cancer Therapy: Homologous Recombination Deficiency as a Predictive Biomarker of Response to PARP Inhibitors
Open access status: An open access version is available from UCL Discovery
DOI: 10.2147/ott.s272199
Publisher version: https://doi.org/10.2147/OTT.S272199
Language: English
Additional information: © 2022 The Author(s). This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License (https://creativecommons.org/licenses/by/3.0/).
Keywords: ovarian cancer, PARP inhibitors, BRCA mutations, homologous recombination deficiency, maintenance therapy
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10157415
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