聚(ADP - 核糖)聚合酶抑制剂的同源重组修复或同源重组缺陷检测:当前观点
Testing for homologous recombination repair or homologous recombination deficiency for poly (ADP-ribose) polymerase inhibitors: A current perspective.
作者信息
Herzog Thomas J, Vergote Ignace, Gomella Leonard G, Milenkova Tsveta, French Tim, Tonikian Raffi, Poehlein Christian, Hussain Maha
机构信息
University of Cincinnati Cancer Center, University of Cincinnati Medical Center, 234 Goodman St, Cincinnati, OH 45219, USA.
Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, Leuven Cancer Institute, Catholic University Leuven, Herestraat 49, 3000 Leuven, Belgium, European Union.
出版信息
Eur J Cancer. 2023 Jan;179:136-146. doi: 10.1016/j.ejca.2022.10.021. Epub 2022 Nov 2.
Poly (ADP-ribose) polymerase inhibitors (PARPis) have demonstrated clinical activity in patients with BRCA1 and/or BRCA2 mutated breast, ovarian, prostate, and pancreatic cancers. Notably, BRCA mutations are associated with defects in the homologous recombination repair (HRR) pathway. This homologous recombination deficiency (HRD) phenotype can also be observed as genomic instability in tumour cells. Accordingly, PARPi sensitivity has been observed in various tumours with HRD, independent of BRCA mutations. Currently, four PARPis are approved by regulatory agencies for the treatment of cancer across multiple tumour types. Most indications are specific to tumours with a confirmed BRCA mutation, mutations in other HRR-related genes, HRD evidenced by genomic instability, or evidence of platinum sensitivity. Regulatory agencies have also approved companion and complementary diagnostics to facilitate patient selection for each PARPi indication. This review aims to summarise the biological basis, clinical validation, and clinical relevance of the available diagnostic methods and assays to assess HRD.
聚(ADP - 核糖)聚合酶抑制剂(PARPis)已在携带BRCA1和/或BRCA2突变的乳腺癌、卵巢癌、前列腺癌和胰腺癌患者中显示出临床活性。值得注意的是,BRCA突变与同源重组修复(HRR)途径的缺陷有关。这种同源重组缺陷(HRD)表型也可在肿瘤细胞中表现为基因组不稳定。因此,在各种具有HRD的肿瘤中均观察到了PARPi敏感性,而与BRCA突变无关。目前,有四种PARPis已获得监管机构批准,用于治疗多种肿瘤类型的癌症。大多数适应症特定于具有确诊BRCA突变、其他HRR相关基因突变、由基因组不稳定证明的HRD或铂敏感性证据的肿瘤。监管机构还批准了伴随诊断和补充诊断方法,以促进针对每种PARPi适应症的患者选择。本综述旨在总结评估HRD的现有诊断方法和检测的生物学基础、临床验证及临床相关性。