Predictive biomarkers for the efficacy of PARP inhibitors in ovarian cancer: an updated systematic review

Abstract Background PARP inhibitors are effective in treating ovarian cancer, especially for BRCA1/2 pathogenic variant carriers and those with HRD (homologous recombination deficiency). Concerns over toxicity and costs have led to the search for predictive biomarkers. We present an updated systemat...

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Main Authors: Ying-Wen Wang, Isaac Allen, Gabriel Funingana, Marc Tischkowitz, Yvonne Walburga Joko-Fru
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:BJC Reports
Online Access:https://doi.org/10.1038/s44276-025-00122-9
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author Ying-Wen Wang
Isaac Allen
Gabriel Funingana
Marc Tischkowitz
Yvonne Walburga Joko-Fru
author_facet Ying-Wen Wang
Isaac Allen
Gabriel Funingana
Marc Tischkowitz
Yvonne Walburga Joko-Fru
author_sort Ying-Wen Wang
collection DOAJ
description Abstract Background PARP inhibitors are effective in treating ovarian cancer, especially for BRCA1/2 pathogenic variant carriers and those with HRD (homologous recombination deficiency). Concerns over toxicity and costs have led to the search for predictive biomarkers. We present an updated systematic review, expanding on a previous ESMO review on PARP inhibitor biomarkers. Methods Following ESMO’s 2020 review protocol, we extended our search to March 31, 2023, including PubMed and clinical trial data. We also reviewed the reference lists of review articles. We conducted a meta-analysis using a random-effects model to evaluate hazard ratios and assess the predictive potential of biomarkers and the effectiveness of PARP inhibitors in survival. Results We found 375 articles, 103 of which were included after screening (62 primary research, 41 reviews). HRD remained the primary biomarker (95%), particularly BRCA1/2 variants (77%). In the non-HRD category, six articles (10%) introduced innovative biomarkers, including ADP-ribosylation, HOXA9 promoter methylation, patient-derived organoids, KELIM, and SLFN11. Discussion Prospective assessment of real-time homologous recombination repair via nuclear RAD51 levels shows promise but needs validation. Emerging biomarkers like ADP-ribosylation, HOXA9 promoter methylation, patient-derived organoids, KELIM, and SLFN11 offer potential but require large-scale validation.
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spelling doaj-art-e1e9509d8f5a484e875a7796e241b8292025-08-20T02:56:12ZengNature PortfolioBJC Reports2731-93772025-03-013111510.1038/s44276-025-00122-9Predictive biomarkers for the efficacy of PARP inhibitors in ovarian cancer: an updated systematic reviewYing-Wen Wang0Isaac Allen1Gabriel Funingana2Marc Tischkowitz3Yvonne Walburga Joko-Fru4Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, Kaohsiung Chang Gung Memorial HospitalDepartment of Public Health and Primary Care, University of CambridgeDepartment of Oncology, University of CambridgeDepartment of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of CambridgeDepartment of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, University of CambridgeAbstract Background PARP inhibitors are effective in treating ovarian cancer, especially for BRCA1/2 pathogenic variant carriers and those with HRD (homologous recombination deficiency). Concerns over toxicity and costs have led to the search for predictive biomarkers. We present an updated systematic review, expanding on a previous ESMO review on PARP inhibitor biomarkers. Methods Following ESMO’s 2020 review protocol, we extended our search to March 31, 2023, including PubMed and clinical trial data. We also reviewed the reference lists of review articles. We conducted a meta-analysis using a random-effects model to evaluate hazard ratios and assess the predictive potential of biomarkers and the effectiveness of PARP inhibitors in survival. Results We found 375 articles, 103 of which were included after screening (62 primary research, 41 reviews). HRD remained the primary biomarker (95%), particularly BRCA1/2 variants (77%). In the non-HRD category, six articles (10%) introduced innovative biomarkers, including ADP-ribosylation, HOXA9 promoter methylation, patient-derived organoids, KELIM, and SLFN11. Discussion Prospective assessment of real-time homologous recombination repair via nuclear RAD51 levels shows promise but needs validation. Emerging biomarkers like ADP-ribosylation, HOXA9 promoter methylation, patient-derived organoids, KELIM, and SLFN11 offer potential but require large-scale validation.https://doi.org/10.1038/s44276-025-00122-9
spellingShingle Ying-Wen Wang
Isaac Allen
Gabriel Funingana
Marc Tischkowitz
Yvonne Walburga Joko-Fru
Predictive biomarkers for the efficacy of PARP inhibitors in ovarian cancer: an updated systematic review
BJC Reports
title Predictive biomarkers for the efficacy of PARP inhibitors in ovarian cancer: an updated systematic review
title_full Predictive biomarkers for the efficacy of PARP inhibitors in ovarian cancer: an updated systematic review
title_fullStr Predictive biomarkers for the efficacy of PARP inhibitors in ovarian cancer: an updated systematic review
title_full_unstemmed Predictive biomarkers for the efficacy of PARP inhibitors in ovarian cancer: an updated systematic review
title_short Predictive biomarkers for the efficacy of PARP inhibitors in ovarian cancer: an updated systematic review
title_sort predictive biomarkers for the efficacy of parp inhibitors in ovarian cancer an updated systematic review
url https://doi.org/10.1038/s44276-025-00122-9
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