酪氨酸激酶抑制剂耐药的分子机制及耐药后治疗策略  

Molecular mechanism and treatment strategy of resistance on tyrosine kinase inhibitor

作　　者：洪菲[1] 闫志凌[1] 徐开林[1] 

机构地区：[1]徐州医学院附属医院血液科,221002

出　　处：《白血病．淋巴瘤》2017年第6期368-371,共4页Journal of Leukemia & Lymphoma

基　　金：国家自然科学基金（81300399）;江苏省重点研发计划（BE2015625）

摘　　要：酪氨酸激酶抑制剂（TKI）治疗慢性粒细胞性白血病（CML）的效果虽然显著,但治疗过程中产生的耐药问题仍无法避免.因此,TKI耐药是CML治疗失败的主要原因之一.据报道,约5%的患者对TKI存在原发性耐药,20%~30%的患者对TKI产生继发性耐药.目前已知的TKI耐药分子机制有bcr-abl过表达、基因突变、DNA修复机制缺陷、ATP-binding cassette（ABC）转运蛋白介导的药物外排、异常信号通路及骨髓微环境等.同时,针对各种耐药机制开发的药物多处于临床前或临床研究阶段,这些药物的研究为克服TKI耐药提供了可能.本文拟对TKI耐药的分子机制及耐药后治疗策略的进展进行综述.Although the efficacy of tyrosine kinase inhibitor （TKI） for the treatment of chronic myeloid leukemia （CML） is obvious, the drug resistance is still inevitable, therefore, TKI drug resistance has become one of the reasons for the failure treatment of CML. According to the literature, about 5 % patients have primary resistance to TKI, and 20 %-30 % patients have secondary resistance to TKI. Current TKI drug resistance molecular mechanisms include the over-expression of bcr-abl, gene mutation, defect of DNA repair mechanism, medicine excretion mediated by ATP-binding cassette translocator, abnormal signaling pathway and bone marrow microenvironment. Meanwhile, the occurrence of drugs, based on the drug resistance mechanism development in preclinical or clinic investigation stage, are likely to provide the possibility for the overcoming of TKI drug resistance. This paper will review the progress of molecular mechanism of TKI drug resistance and the therapy strategy after drug resistance.

关 键 词：白血病 髓系 慢性 酪氨酸激酶抑制剂 突变 耐药 

分 类 号：R733.7[医药卫生—肿瘤]