靶向抑制BCR-ABL肿瘤蛋白表达的药物研究进展

Progress in the development of molecular therapies targeting BCR-ABL oncoprotein expression

反义核酸技术、RNA干扰技术及核酶技术等靶向抑制BCR-ABL mRNA的药物,在体外实验中显示了一定的治疗作用,但缺乏体内研究资料,目前尚未进入临床应用阶段。影响BCR-ABL肿瘤蛋白稳定性的热休克蛋白90抑制剂与伊马替尼联合应用可以克服突变细胞株的耐药,并显示对慢性髓性白血病(CML)干细胞的抑制效应,在BCR-ABL阳性白血病的治疗中显示出良好的应用前景,值得进一步研究开发。

Molecular therapies targeting mRNA of BCR-ABL expression, including Anti-sense oligonucleotides, RNA interference and ribozymes technique, have presented therapeutic efficacy in vitro, but the limited in vivo data limited their potential for clinical usage. Combined imatinib and heat shock protein 90（HSP90） inhibition, which alters the protein stability of BCR-ABL tyrosine kinases overcomes the resistance of mutated cell lines and even shows inhibitory effect on leukemic stem cells in chronic myelogenous leukemia. Preliminary data showed its perspective application in treating BCR-ABL positive leukemia and therefore deserves further investigation and development.