Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University (Rangsit Campus), Pathumtani, 12121, Thailand.
Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University (Rangsit Campus), Pathumtani, 12121, Thailand.
Cancer Chemother Pharmacol. 2019 Nov;84(5):959-975. doi: 10.1007/s00280-019-03932-0. Epub 2019 Sep 4.
Not all patients respond well to cancer chemotherapy. One of the most important factors contributing to treatment response (efficacy and toxicity) is genetic determinant. The current systematic review aims to provide current status of the information on the genetic contribution of genes encoding drug transport proteins and drug metabolizing enzyme, cytochrome P450 (CYP), and relationship with clinical outcomes of cancer chemotherapy.
The literature search was performed through PubMed and ScienceDirect databases. One hundred and four research articles that fulfilled the inclusion criteria and had none of the exclusion criteria were included in the analysis.
Various studies reported conflicting results for the polymorphisms of the major genes and association with treatment outcomes in patients with various types of cancer. Nevertheless, among the investigated gene polymorphisms, it appears that the 1236C>T, 3435C>T and 2677 G>T/A SNPs of the drug transporter gene ABCB1 were the most promising determinants of clinical outcomes. Although both 1236C>T and 3435C>T polymorphism are synonymous SNPs, several studies have demonstrated that not all synonymous SNPs are silent. Therefore, using the haplotype (1236C>T, 2677G>T, and 3435C>T) analysis rather than a single SNP may be a more useful approach for phenotype prediction. Some of the patients with variants of CYP genes were associated with unsatisfactory treatment response (efficacy and toxicity), suggesting that these variants may be associated with either reduction or absence of CYP enzyme activity.
The controversial results may be due to several factors including difference in populations studied, sample size, tumor sites and stages, chemotherapeutic drug regimens, and evaluation parameters for efficacy and/or toxicity. Before the information can be successfully applied to individualized cancer chemotherapy, further studies should be focused on these promising genetic markers and their association with clinical outcomes using standardized protocols.
并非所有癌症患者对化疗的反应都良好。影响治疗反应（疗效和毒性）的最重要因素之一是遗传决定因素。本系统评价旨在提供有关编码药物转运蛋白和药物代谢酶细胞色素 P450（CYP）的基因的遗传贡献以及与癌症化疗临床结局的关系的最新信息。
通过 PubMed 和 ScienceDirect 数据库进行文献检索。纳入符合纳入标准且无排除标准的 104 篇研究文章进行分析。
各种研究报告了主要基因的多态性与各种类型癌症患者治疗结果之间的不一致结果。然而，在所研究的基因多态性中，似乎药物转运基因 ABCB1 的 1236C>T、3435C>T 和 2677 G>T/A SNP 是最有前途的临床结局决定因素。尽管 1236C>T 和 3435C>T 多态性均为同义 SNP，但多项研究表明并非所有同义 SNP 均为沉默。因此，与使用单个 SNP 相比，使用单体型（1236C>T、2677G>T 和 3435C>T）分析可能是预测表型的更有用方法。一些 CYP 基因变异的患者与治疗反应（疗效和毒性）不理想有关，这表明这些变异可能与 CYP 酶活性的降低或缺失有关。
有争议的结果可能是由于多种因素引起的，包括研究人群、样本量、肿瘤部位和分期、化疗药物方案以及疗效和/或毒性的评估参数的差异。在成功将这些信息应用于个体化癌症化疗之前，应使用标准化方案进一步研究这些有前途的遗传标记物及其与临床结局的关系。
