Molecular mechanism and treatment strategy of resistance on tyrosine kinase inhibitor

VernacularTitle:酪氨酸激酶抑制剂耐药的分子机制及耐药后治疗策略
Author: Fei HONG ; Zhiling YAN
Keywords: Leukemia,myelogenous,chronic; Tyrosine kinase inhibitor; Mutation; Drug resistance
From: Journal of Leukemia & Lymphoma 2017;26(6):368-371
CountryChina
Language:Chinese
Abstract: 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.