针对T315I突变的Bcr-Abl酪氨酸激酶抑制剂研究进展

Advances in Research on Bcr-Abl Tyrosine Kinase Inhibitors against T315I Mutation1,2221

BCR-ABL是一种由bcr基因和c-abl原癌基因融合产生的致癌基因。该基因表达的Bcr–Abl癌蛋白是慢性粒细胞白血病的病理学基础。因此研发选择性的Bcr–Abl酪氨酸激酶抑制剂成为治疗慢性粒细胞白血病的一种有效策略。目前已有数个Bcr–Abl酪氨酸激酶抑制剂获准上市。然而,Abl激酶结构域的突变或其他原因导致肿瘤耐药性的出现,其中T315I突变是最重要的突变之一,引发的耐药性更是难以克服。重点介绍了针对T315I突变的Bcr–Abl酪氨酸激酶抑制剂的研究进展。

BCR-ABL is an oncogene that arises from the fusion of the bcr gene and the c-abl proto-oncogene. The Bcr-Abl oncoprotein is believed to be the primary cause of chronic myelogenous leukemia （CML）. Thus, the development of selective Bcr-Abl kinase inhibitors is an attractive strategy to treat CML. Several Bcr-Abl tyrosine kinase inhibitors （Bcr-Abl TKIs） have been approved recently. However, multiple drug resistance of tumor cells against the existing Bcr-Abl TKIs has emerged due to the mutations in the Abl kinase domain or other reasons. Among them the T315I mutation is the most difficult one to be treated. The recent progress in research on Bcr-Abl TKIs against T3151 mutation has been reviewed in this paper.