Department of Clinical and Molecular Pathology, Institute of Translational and Molecular Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic.
Department of Pathology and Molecular Pathology, University Hospital, Zurich, Switzerland.
Int J Cancer. 2017 Oct 1;141(7):1286-1294. doi: 10.1002/ijc.30764. Epub 2017 May 19.
Targeting deficient mechanisms of cellular DNA repair still represents the basis for the treatment of the majority of solid tumors, and increased DNA repair capacity is a hallmark mechanism of resistance not only to DNA-damaging treatments such as cytotoxic drugs and radiotherapy, but also to small molecule targeted drugs such as inhibitors of poly-ADP ribose polymerase (PARP). Hence, there is substantial medical need for potent and convenient biomarkers of individual response to DNA-targeted treatment in personalized cancer care. RAD51 is a highly conserved protein that catalyzes DNA repair via homologous recombination, a major DNA repair pathway which directly modulates cellular sensitivity to DNA-damaging treatments. The clinical and biological significance of RAD51 protein expression is still under investigation. Pre-clinical studies consistently show the important role of nuclear RAD51 immunoreactivity in chemo- and radioresistance. Validating data from clinical trials however is limited at present, and some clinical studies show controversial results. This review gives a comprehensive overview on the current knowledge about the prognostic and predictive value of RAD51 protein expression and genetic variability in patients with solid malignancies.
针对细胞 DNA 修复机制缺陷仍然是治疗大多数实体瘤的基础，而增加 DNA 修复能力不仅是对细胞毒性药物和放射治疗等 DNA 损伤治疗产生耐药性的标志机制，也是对多聚 ADP 核糖聚合酶 (PARP) 抑制剂等小分子靶向药物产生耐药性的标志机制。因此，在个性化癌症治疗中，需要有力且方便的个体对 DNA 靶向治疗反应的生物标志物。RAD51 是一种高度保守的蛋白质，通过同源重组催化 DNA 修复，这是一种主要的 DNA 修复途径，直接调节细胞对 DNA 损伤治疗的敏感性。RAD51 蛋白表达的临床和生物学意义仍在研究中。临床前研究一致表明核 RAD51 免疫反应在化疗和放疗耐药性中的重要作用。然而，目前验证临床试验数据的工作有限，并且一些临床研究显示出有争议的结果。这篇综述全面概述了目前关于实体恶性肿瘤患者 RAD51 蛋白表达和遗传变异的预后和预测价值的知识。
