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Background <p>PARP inhibitors are effective in treating ovarian cancer, especially for <i>BRCA1/2</i> 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.</p> Methods <p>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.</p> Results <p>We found 375 articles, 103 of which were included after screening (62 primary research, 41 reviews). HRD remained the primary biomarker (95%), particularly <i>BRCA1/2</i> variants (77%). In the non-HRD category, six articles (10%) introduced innovative biomarkers, including ADP-ribosylation, <i>HOXA9</i> promoter methylation, patient-derived organoids, KELIM, and <i>SLFN11</i>.</p> Discussion <p>Prospective assessment of real-time homologous recombination repair via nuclear RAD51 levels shows promise but needs validation. Emerging biomarkers like ADP-ribosylation, <i>HOXA9</i> promoter methylation, patient-derived organoids, KELIM, and <i>SLFN11</i> offer potential but require large-scale validation.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月11日

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  • Ying-Wen Wang,
  • Isaac Allen,
  • Gabriel Funingana,
  • Marc Tischkowitz,
  • Yvonne Walburga Joko-Fru

摘要

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.