Isomura Minoru, Miki Yoshio
Genome Center of the Japanese Foundation for Cancer Research.
Gan To Kagaku Ryoho. 2005 Nov;32(12):1908-13.
In recent years, pharmacogenomics have received much attention from the increased expectations for so-called order-made medicine. It is experientially clear that inter-individual differences exist in the degree of efficacy and occurrence of adverse effects. These inter-individual differences are observed not only among anticancer chemotherapeutics but in almost all drugs. Several studies have revealed that genetic factors are involved in these inter-individual differences. To date, the relationships have been revealed between adverse effects of some anticancer drugs and polymorphisms of drug metabolizing genes. Such relationships include 5-FU and DPYD gene, methotorexate and MTHFR gene, irinotecan and UGT 1A1 gene and 6-MP and TPMT gene. By using information on these polymorphisms, it will be possible to predict the occurrence of adverse effects before using anticancer drugs. In particular, information on polymorphisms related to the possibly adverse effects of irinotecan is now given in its package leaflet. This means that order-made medicine is a step closer. In this review, we discuss the relationships between polymorphisms of genes and the adverse effects of anticancer drugs. Furthermore, we want to suggest the direction of further pharmacogenomic studies with an eye to the realization of order-made medicine.
近年来,药物基因组学因人们对所谓定制药物的期望不断提高而备受关注。经验表明,个体之间在疗效程度和不良反应发生率方面存在差异。这些个体差异不仅在抗癌化疗药物中存在,几乎在所有药物中都能观察到。多项研究表明,遗传因素与这些个体差异有关。迄今为止,已经揭示了一些抗癌药物的不良反应与药物代谢基因多态性之间的关系。这些关系包括5-氟尿嘧啶与DPYD基因、甲氨蝶呤与MTHFR基因、伊立替康与UGT 1A1基因以及6-巯基嘌呤与TPMT基因。通过利用这些多态性信息,在使用抗癌药物之前就有可能预测不良反应的发生。特别是,伊立替康可能产生的不良反应相关多态性信息现在已在其药品说明书中给出。这意味着定制药物又向前迈进了一步。在这篇综述中,我们讨论了基因多态性与抗癌药物不良反应之间的关系。此外,我们希望着眼于定制药物的实现,提出进一步药物基因组学研究的方向。