Division of Clinical Pharmacology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Oncologist. 2011;16(6):820-34. doi: 10.1634/theoncologist.2010-0259. Epub 2011 May 31.
Equivalent drug doses in anticancer chemotherapy may lead to wide interpatient variability in drug response reflected by differences in treatment response or in severity of adverse drug reactions. Differences in the pharmacokinetic (PK) and pharmacodynamic (PD) behavior of a drug contribute to variation in treatment outcome among patients. An important factor responsible for this variability is genetic polymorphism in genes that are involved in PK/PD processes, including drug transporters, phase I and II metabolizing enzymes, and drug targets, and other genes that interfere with drug response. In order to achieve personalized pharmacotherapy, drug dosing and treatment selection based on genotype might help to increase treatment efficacy while reducing unnecessary toxicity. We present a series of four reviews about pharmacogenetic variability in anticancer drug treatment. This is the second review in the series and is focused on genetic variability in genes encoding drug transporters (ABCB1 and ABCG2) and phase I drug-metabolizing enzymes (CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, DPYD, CDA and BLMH) and their associations with anticancer drug treatment outcome. Based on the literature reviewed, opportunities for patient-tailored anticancer therapy are presented.
在癌症化疗中，等效药物剂量可能会导致药物反应的个体间差异很大，表现在治疗反应或药物不良反应的严重程度上的差异。药物的药代动力学（PK）和药效学（PD）行为的差异导致了患者之间治疗结果的变化。导致这种变异性的一个重要因素是参与 PK/PD 过程的基因中的遗传多态性，包括药物转运体、I 期和 II 期代谢酶以及药物靶点，以及其他干扰药物反应的基因。为了实现个体化的药物治疗，基于基因型的药物剂量和治疗选择可能有助于提高治疗效果，同时减少不必要的毒性。我们呈现了一系列关于癌症药物治疗中药物遗传学变异性的四篇综述。这是该系列中的第二篇综述，重点介绍了编码药物转运体（ABCB1 和 ABCG2）和 I 期药物代谢酶（CYP2B6、CYP2C8、CYP2C9、CYP2C19、CYP2D6、CYP3A4、CYP3A5、DPYD、CDA 和 BLMH）的基因中的遗传变异性及其与癌症药物治疗结果的关联。基于回顾的文献，提出了针对患者的癌症治疗机会。
