Desai Apurva A, Innocenti Federico, Ratain Mark J
Department of Medicine, The University of Chicago, Chicago, IL, USA.
Oncogene. 2003 Sep 29;22(42):6621-8. doi: 10.1038/sj.onc.1206958.
Interindividual differences in the toxicity and response to anticancer therapies are currently observed for essentially all available treatment regimens. Such 'unpredictable' drug responses are particularly dangerous in the context of anticancer agents that have narrow therapeutic indices. Pharmacogenomics attempts to elucidate the inherited basis of interindividual differences in drug response, with the eventual goal of minimizing such variability through the use of 'individualized' treatments. There are several emerging examples of genetic polymorphisms of drug-metabolizing enzymes, DNA repair genes and drug targets that have been shown to influence the toxicity and efficacy of anticancer treatment. This review discusses the role of genetic variants of UGT1A1, TS and EGFR to exemplify the potential impact of phramacogenomics on the field of anticancer therapeutics.
目前，对于几乎所有可用的治疗方案，都观察到了个体间在抗癌治疗毒性和反应方面的差异。在治疗指数较窄的抗癌药物背景下，这种“不可预测”的药物反应尤其危险。药物基因组学试图阐明个体间药物反应差异的遗传基础，最终目标是通过使用“个体化”治疗来最小化这种变异性。有几个新出现的例子表明，药物代谢酶、DNA修复基因和药物靶点的基因多态性会影响抗癌治疗的毒性和疗效。本综述讨论了UGT1A1、TS和EGFR基因变异的作用，以举例说明药物基因组学在抗癌治疗领域的潜在影响。
