INSERM U981, Department of Medicine, Université Paris-Sud XI-Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France.
Nat Rev Clin Oncol. 2012 Feb 14;9(3):144-55. doi: 10.1038/nrclinonc.2012.3.
The tumor genome is commonly aberrant as a consequence of mutagenic insult and incomplete DNA repair. DNA repair as a therapeutic target has recently received considerable attention owing to the promise of drugs that target tumor-specific DNA-repair enzymes and potentiate conventional cytotoxic therapy through mechanism-based approaches, such as synthetic lethality. Treatment for non-small-cell lung cancer (NSCLC) consists mainly of platinum-based chemotherapy regimens and improvements are urgently needed. Optimizing treatment according to tumor status for DNA-repair biomarkers, such as ERCC1, BRCA1 or RRM1, could predict response to platinum, taxanes and gemcitabine-based therapies, respectively, and might improve substantially the response of individual patients' tumors. Finally, recent data on germline variation in DNA-repair genes may also be informative. Here, we discuss how a molecular and functional DNA-repair classification of NSCLC may aid clinical decision making and improve patient outcome.
肿瘤基因组通常由于诱变损伤和不完全的 DNA 修复而异常。由于靶向肿瘤特异性 DNA 修复酶的药物以及通过基于机制的方法（如合成致死）增强常规细胞毒性治疗的药物有希望，因此 DNA 修复作为治疗靶点最近受到了相当多的关注。非小细胞肺癌 (NSCLC) 的治疗主要包括铂类化疗方案，迫切需要改进。根据 ERCC1、BRCA1 或 RRM1 等 DNA 修复生物标志物的肿瘤状态优化治疗，可以分别预测对铂类、紫杉烷类和吉西他滨类治疗的反应，并且可能大大改善个体患者肿瘤的反应。最后，最近关于 DNA 修复基因种系变异的数据也可能具有启发性。在这里，我们讨论了 NSCLC 的分子和功能 DNA 修复分类如何帮助临床决策并改善患者预后。
