PARP抑制剂治疗卵巢癌疗效的预测生物标志物：一项更新的系统评价
Predictive biomarkers for the efficacy of PARP inhibitors in ovarian cancer: an updated systematic review.
作者信息
Wang Ying-Wen, Allen Isaac, Funingana Gabriel, Tischkowitz Marc, Joko-Fru Yvonne Walburga
机构信息
Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
出版信息
BJC Rep. 2025 Mar 11;3(1):14. doi: 10.1038/s44276-025-00122-9.
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.
背景
聚（ADP-核糖）聚合酶（PARP）抑制剂在治疗卵巢癌方面有效，尤其是对携带BRCA1/2致病变异的患者以及那些存在同源重组缺陷（HRD）的患者。对毒性和成本的担忧促使人们寻找预测性生物标志物。我们进行了一项更新的系统评价，在之前欧洲肿瘤内科学会（ESMO）关于PARP抑制剂生物标志物的综述基础上进行了扩展。
方法
按照ESMO 2020年的综述方案，我们将检索范围扩展至2023年3月31日，包括PubMed和临床试验数据。我们还查阅了综述文章的参考文献列表。我们使用随机效应模型进行荟萃分析，以评估风险比，并评估生物标志物的预测潜力以及PARP抑制剂在生存方面的有效性。
结果
我们找到了375篇文章，经过筛选后纳入了103篇（62篇原始研究，41篇综述）。HRD仍然是主要的生物标志物（95%），尤其是BRCA1/2变异（77%）。在非HRD类别中，六篇文章（10%）引入了创新的生物标志物，包括ADP-核糖基化、HOXA9启动子甲基化、患者来源的类器官、KELIM和SLFN11。
讨论
通过细胞核RAD51水平对实时同源重组修复进行前瞻性评估显示出前景，但需要验证。ADP-核糖基化、HOXA9启动子甲基化、患者来源的类器官、KELIM和SLFN11等新兴生物标志物具有潜力，但需要大规模验证。
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