Department of Clinical, Social, & Administrative Sciences, University of Michigan College of Pharmacy, Ann Arbor, MI, USA.
Pharmacogenomics. 2013 Jul;14(9):1065-84. doi: 10.2217/pgs.13.90.
Paclitaxel is a highly effective chemotherapeutic agent used in a variety of solid tumors. Some paclitaxel-treated patients experience the intended therapeutic response with manageable side effects, while others have minimal response and/or severe toxicity. This variability in treatment outcome is partially determined by variability in drug exposure (pharmacokinetics) and by patient and tumor sensitivity (pharmacodynamics). Both pharmacokinetics and pharmacodynamics are dictated in part by common variants in the germline genome, known as SNPs. This article reviews the published literature on paclitaxel pharmacogenetics in cancer, focusing primarily on polymorphisms in genes relevant to paclitaxel pharmacokinetics and discusses preliminary work on pharmacodynamic genes and genome-wide association studies.
紫杉醇是一种广泛应用于多种实体瘤的高效化疗药物。部分接受紫杉醇治疗的患者疗效显著,副作用可耐受,而另一些患者则疗效甚微或毒性反应严重。这种治疗效果的差异部分归因于药物暴露(药代动力学)的差异,以及患者和肿瘤的敏感性(药效动力学)差异。药代动力学和药效动力学在一定程度上受种系基因组中常见变异(即 SNPs)的影响。本文综述了癌症紫杉醇药物遗传学的相关文献,重点关注与紫杉醇药代动力学相关的基因多态性,并讨论了药效动力学基因和全基因组关联研究的初步工作。