药物蛋白核苷酸多态性对靶向药物伊马替尼敏感性的影响

The effect of drug transporter gene polymorphisms on susceptibility to imatinib in chronic myelogenous leukemia

作为第一代酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs),伊马替尼是临床上用于治疗慢性粒细胞白血病(chronicmyelogenous leukemia,CML)的一线药物。然而在临床治疗中,部分患者口服伊马替尼后疗效并不理想,出现伊马替尼耐药的情况。伊马替尼耐药机制比较复杂,除了TKIs的突变,国内外研究还发现ABC家族转运蛋白(ATP-binding cassette transporters,ABC),有机阴离子转运体及有机阳离子转运体对伊马替尼药代动力学与药效学具有影响。本文主要从影响伊马替尼疗效的药物转运体基因多态性对伊马替尼治疗CML患者个体疗效差异予以综述,为进一步的临床研究提供参考依据。

As a first generation tyrosine kinase inhibitor, imatinib is the gold standard drug for the clinical treatment of chronic myelogenous leukemia. However, interindividual differences in resistance and response to imatinib have been widely observed. In vivo and in vitro studies have confirmed that ATP-binding cassette transporters, organic cation transporters, and organic anion transporting polypeptides have a large effect on imatinib pharmacokinetics and pharmacodynamics. In addition, the gene polymorphisms of drug transporters can directly or indirectly influence the intracellular concentration of imatinib, resulting in differences in treatment efficacy among chronic myelogenous leukemia patients. This review profiles the effect of drug transporter gene polymorphisms on susceptibility to imatinib in chronic myelogenous leukemia so as to provide reference to further clinical researches.