Bcr-Abl酪氨酸激酶抑制剂联合用药治疗慢性粒细胞白血病研究进展

以伊马替尼为代表的酪氨酸激酶抑制剂对慢性粒细胞白血病(CML)的治疗产生了重要影响,但其耐药性已成为CML治疗领域的关键问题。伊马替尼、尼洛替尼、达沙替尼以及普纳替尼等Bcr-Abl酪氨酸激酶抑制剂与其他药物联合使用,可以协同抑制Bcr-Abl及其磷酸化蛋白的表达,显著降低STAT5、CRKL、ERK5等信号通路的磷酸化水平,改善肿瘤微环境,降低肿瘤细胞多药耐药性,已在基础研究和临床Ⅰ期研究中取得阶段性成果,为治疗CML提供新策略。

Research progress of Bcr-Abl tyrosine kinase inhibitors combined with other drugs for chronic myelogenous leukemia

Tyrosine kinase inhibitors(TKI)represented by imatinib make significant influence on chronic myelogenous leukemia(CML)therapy.However,drug resistance of tumor cells against the existing Bcr-Abl TKIs has emerged as a key issue.Combined treatment with imatinib,nilotinib,dasatinib or ponatinib with other drugs caused synergistic inhibition of Bcr-Abl and reduction of its phosphorylation,and significantly reduce the phosphorylation levels of signal pathways with STAT5,CRKL and ERK5,which improved the tumor microenviroment and reduced the multidrug resistance of tumor cells.These results from basic research and phase Ⅰ clinic research will benefit for the CML therapy.