小细胞肺癌患者铂类化疗 所致周围神经毒性与SNP相关性

小细胞肺癌(SCLC)患者的治疗正在发生改变,但含铂双药联合化疗仍然是大多数SCLC患者的治疗基础。SCLC患者在接受化学治疗同时,还需忍受药物毒性引起的周围神经毒性(peripheral neurotoxicity,PN)等相关毒副作用。周围神经毒性主要表现为刺痛、麻木、虚弱或灼痛,且呈剂量依赖性。药物基因组学现已发展为一种有效的研究方法,目前可以利用基因组学获得关于药物反应的个体间差异的相关遗传信息,从而避免周围神经毒性的发生,以达到精准治疗的目的。单核苷酸多态性(single nucleotide polymorphism,SNP)定义为在基因组水平上由于单个核苷酸的变异而导致的DNA序列多态性。人类可遗传变异中最多的就是SNP,甚至在已知的所有多态性中90%以上都是单核苷酸变异。本文就小细胞肺癌患者铂类药物引起的周围神经毒性与相关GSTP1和GSTM1基因、ERCC1基因、ABCC2和ABCC4基因、SCNAs基因、CYP2C8基因、AGXT基因的SNP之间的关系作一简要综述。

Correlation between peripheral neurotoxicity caused by platinum-based chemotherapy and SNP in patients with small cell lung cancer

Abstract: Although the treatment of small cell lung cancer (SCLC) is changing, but platinum-containing dual-drug combination chemotherapy remains the basis of treatment for most SCLC patients. In patients with SCLC, the associated toxic side effects such as peripheral neurotoxicity (PN) are inevitable at the same time as the chemotherapy is given. Peripheral neurotoxicity is mainly manifested as sting, numbness, weakness or burning pain in a dose-dependent manner. Pharmacogenomics has now evolved into an effective method, which can obtain genetic information about inter-individual differences in drug response and avoid the development of peripheral neurotoxicity to achieve precise treatment. Single nucleotide polymorphism (SNP) is defined as a DNA sequence polymorphism at the genomic level due to a single nucleotide variation. The most common in human heritable variation is the SNP, and even more than 90% of all known polymorphisms are single nucleotide variants. This article briefly reviews the relationship between peripheral neurotoxicity induced by platinum drugs and related SNPs of GSTP1 gene, GSTM1 gene, ERCC1 gene, ABCC2 gene, ABCC4 gene, SCNAs gene, CYP2C8 gene and AGXT gene in small cell lung cancer patients.