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首页> 外文期刊>Mutation Research. Reviews in Mutation Research >Contribution of genetic factors to platinum-based chemotherapy sensitivity and prognosis of non-small cell lung cancer
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Contribution of genetic factors to platinum-based chemotherapy sensitivity and prognosis of non-small cell lung cancer

机译：遗传因素对非小细胞肺癌的铂化疗敏感性和预后的贡献

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Graphical abstract Display Omitted Abstract Although platinum-based chemotherapy remains the standard treatment for advanced NSCLC patients, clinical outcomes are poor and most patients develop high-grade toxicities. Genetic factors, such as single nucleotide polymorphisms (SNPs) involved in platinum pharmacodynamics, metabolism and mechanism of action, may account for inter-individual differences shown in effectiveness and toxicity. Polymorphisms in genes involved in DNA repair and others such as PI3K/PTEN/AKT and TGF-β pathways have been demonstrated to be associated with response, survival and toxicity in advanced NSCLC patients treated with platinum-based chemotherapy. Other cellular processes, like DNA methylation and proliferation have been connected with clinical outcome for platinum-based chemotherapy regimens through folate metabolism and cytokine signaling. The influence of gene polymorphisms in the NER pathway on clinical outcome has been extensively investigated in advanced NSCLC patients treated with platinum-based chemotherapy but contradictory results have been reported. The most recent and thorough meta-analyses have failed to show an association between ERCC1 C118T/C8092A and ERCC5 rs1047768 polymorphisms and response to platinum based chemotherapy. However, other polymorphisms in ERCC2 (Lys751Gln and Asp312Asn) and ERCC5 (rs2094258 and rs2296147) and have been related with overall survival (OS) and progression-free survival (PFS), respectively. The Arg194Trp and Gln399Arg polymorphisms in XRCC1 , have also been extensively investigated. Their effects seem to be dependent on ethnicity, and recent meta-analyses have confirmed an association with response in Asian but not in Caucasian patients. The influence on overall response rate (ORR) of the rs861539 polymorphism in XRCC3, part of (DSB) repair pathway, has also been confirmed in a meta-analysis. Finally, SNPs in genes coding proteins of the p53, PI3K, TGF-β, membrane transporters, gluthatione metabolism enzymes and cytokine pathways have been less extensively investigated. Some polymorphisms have been reported to be associated with toxicity or clinical outcome, but data generally come from a limited number of studies and need to be confirmed.
机译：图形抽象显示省略摘要虽然基于铂的化疗仍然是先进的NSCLC患者的标准治疗，但临床结果差，大多数患者开发高档毒性。遗传因素，例如参与铂药物动力学，代谢和作用机制的单一核苷酸多态性（SNP），可能占有效性和毒性的间间差异。已经证明了参与DNA修复和其他如PI3K / PTEN / AKT和TGF-β途径如PI3K / PTEN / AKT和TGF-β途径的多态性，以与用铂类化疗治疗的先进NSCLC患者的反应，存活和毒性相关。与DNA甲基化和增殖一样的其他细胞方法已通过叶子代谢和细胞因子信号传导与基于铂的化疗方案的临床结果与临床结果相连。在铂类化疗治疗的晚期NSCLC患者中，在临床结果对临床结果中的基因多态性对临床结果的影响已被报告。最近和彻底的荟萃分析未能在ERCC1 C118T / C8092A和ERCC5 RS1047768多态性和对铂基化疗的反应之间进行关联。然而，ERCC2（LYS751GLN和ASP312ASN）和ERCC5（RS2094258和RS2296147）中的其他多态性分别与整体存活（OS）和无进展的存活（PFS）有关。 XRCC1中的ARG194TRP和GLN399ARG多态性也得到了广泛的调查。他们的效果似乎依赖种族，最近的荟萃分析已经证实了亚洲患者响应的关联，但不在白种人患者中。在META分析中也已经证实了在XRCC3中的RS861539多态性的对XRCC3，部分（DSB）修复途径的一部分对抗率（ORR）的影响。最后，在P53，PI3K，TGF-β，膜转运蛋白，葡萄醛代谢酶和细胞因子途径的基因中的SNP已经不太广泛地研究。据报道一些多态性与毒性或临床结果有关，但数据通常来自有限数量的研究，并且需要确认。

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