Daly Ann K
School of Clinical and Laboratory Sciences, Newcastle University Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Curr Opin Drug Discov Devel. 2007 Jan;10(1):29-36.
The pharmacogenetics of either individual patients or tumors has been used to aid the progress of personalized medicine to generate antitumor drugs (eg, trastuzamab and erlotinib) that are active against tumors expressing particular growth factor receptors. Outside the field of cancer therapeutics, pharmacogenetic tests have been introduced to detect patient genotypes with the aim of individualizing existing treatments. For example, the analysis of thiopurine S-methyltransferase genotypes enables the prediction of toxicity in patients to be treated with either 6-mercaptopurine or azathioprine, while the uridine 5'-diphosphoglucuronosyl-transferase 1A1 genotype may predict irinotecan toxicity. There is a large body of information concerning cytochrome P450 (CYP) polymorphisms and their relationship with drug toxicity and response; however, currently, there is limited use of CYP genotypes to individualize treatments. It is now well recognized that the CYP2C9 genotype, when combined with the genotype for vitamin K epoxide reductase complex subunit 1, is predictive of dose requirement for oral anticoagulants, a fact that is likely to have clinical utility. There is also potential to individualize treatments with certain drugs on the basis of CYP2D6, CYP2C19 and CYP3A5 genotypes. Studies on genes encoding drug receptors in relation to individualized prescription have been limited but there is increasing information on the relationship between response to beta2-adrenoceptor agonists and the genotype for the beta2-adrenoceptor gene. The introduction of pharmacogenetic tests into routine healthcare requires both a demonstration of cost-effectiveness and the availability of appropriate accessible testing systems.
个体患者或肿瘤的药物遗传学已被用于推动个性化医疗的发展,以研发出对表达特定生长因子受体的肿瘤有效的抗肿瘤药物(如曲妥珠单抗和厄洛替尼)。在癌症治疗领域之外,已经引入了药物遗传学检测来检测患者基因型,目的是使现有治疗个体化。例如,对硫嘌呤S - 甲基转移酶基因型的分析能够预测接受6 - 巯基嘌呤或硫唑嘌呤治疗的患者的毒性,而尿苷5'-二磷酸葡萄糖醛酸基转移酶1A1基因型可能预测伊立替康的毒性。有大量关于细胞色素P450(CYP)多态性及其与药物毒性和反应关系的信息;然而,目前CYP基因型在个体化治疗中的应用有限。现在人们已经充分认识到,CYP2C9基因型与维生素K环氧化物还原酶复合体亚基1的基因型相结合时,可预测口服抗凝剂的剂量需求,这一事实可能具有临床实用性。基于CYP2D6、CYP2C19和CYP3A5基因型对某些药物进行个体化治疗也具有潜力。关于与个体化处方相关的药物受体编码基因的研究有限,但关于β2 - 肾上腺素能受体激动剂反应与β2 - 肾上腺素能受体基因基因型之间关系的信息越来越多。将药物遗传学检测引入常规医疗保健既需要证明其成本效益,也需要有合适的可及检测系统。