Bcl-2抑制剂BH3模拟物在血液系统恶性肿瘤治疗中的研究进展

Advances in treatment of hematological malignancies with Bcl-2 inhibitor:BH3 mimetic

细胞凋亡异常是血液系统恶性肿瘤发生的主要机制之一,而Bcl-2家族蛋白在细胞凋亡调节中起着关键作用,因此靶向Bcl-2家族蛋白药物的研发已成为当前药物开发领域的一大热点。其中BH3模拟物是一类靶向作用于Bcl-2家族蛋白的新型抗肿瘤药物,该类药物可以模拟BH3-only蛋白的BH3结构域与Bcl-2家族蛋白成员相互作用,置换并释放促凋亡蛋白,诱导细胞凋亡,从而实现抗肿瘤作用。近年来研究显示BH3模拟物如ABT-263和ABT-199等在多种血液系统肿瘤中已显示出良好的应用前景,ABT-199单药或与其他药物联用治疗均能提高治疗效果,延长患者的生存时间。

Abnormal apoptosis is one of the main mechanisms of hematological malignancies, and Bcl-2 family proteins play a key role in the regulation of apoptosis. Therefore, the development of drugs targeting Bcl-2 family proteins has been developed. It has become a hot spot in the current drug development field. Among them, BH3 mimetic is a novel anti-tumor drug targeting Bcl-2 family proteins, which can mimic the BH3 domain of BH3-only protein and interact with Bcl-2 family protein members, then replace and release pro-apoptotic proteins induce apoptosis, thereby achieving anti-tumor effects. The BH3 mimetic such as ABT-263 and ABT-199 have shown good application prospects in various hematological tumors in recent studies,especially that ABT-199 alone or in combination with drugs can improve the therapeutic effect and extend the survival time of patients.