Chen Sylvia, Sutiman Natalia, Chowbay Balram
Laboratory of Clinical Pharmacology, Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, Singapore.
SingHealth Clinical Pharmacology, Singapore.
Pharmacogenomics. 2016 Nov;17(17):1941-1955. doi: 10.2217/pgs-2016-0124. Epub 2016 Nov 2.
The use of imatinib in the treatment of BCR-ABL-positive chronic myeloid leukemia and gastrointestinal stromal tumors has significantly improved survival outcomes in patients afflicted by these malignancies. However, a substantial proportion of imatinib-treated patients still experience treatment failure. Suboptimal concentrations of imatinib have been postulated to contribute at least partially to the development of resistance against imatinib. Indeed, variations in the genes encoding drug transporters have been reported to markedly influence imatinib disposition and treatment outcomes in various populations. This review aims to consolidate and critically assess the studies conducted to date which have investigated the influence of pharmacogenetic variants in drug transporters on the disposition of imatinib and treatment outcomes in Asians and other populations.
伊马替尼用于治疗BCR-ABL阳性慢性髓性白血病和胃肠道间质瘤,显著改善了罹患这些恶性肿瘤患者的生存结局。然而,相当一部分接受伊马替尼治疗的患者仍经历治疗失败。据推测,伊马替尼浓度未达最佳至少部分导致了对伊马替尼耐药的产生。事实上,已有报道称编码药物转运蛋白的基因变异会显著影响不同人群中伊马替尼的处置和治疗结局。本综述旨在汇总并严格评估迄今开展的研究,这些研究调查了药物转运蛋白中的药物遗传学变异对亚洲人和其他人群中伊马替尼处置及治疗结局的影响。