BCR抑制剂在慢性淋巴细胞白血病治疗中的研究进展

目的:B细胞受体(BCR)信号通路的过度活化与慢性淋巴细胞白血病(CLL)的发生、发展密切相关。Bruton酪氨酸激酶(BTK)、磷脂酰肌醇-3激酶(PI3K)和脾酪氨酸激酶(SYK)作为该通路的关键激酶,已成为CLL靶向治疗的研究热点。在过去的10年中,针对BCR通路治疗CLL的靶向药物,如BTK抑制剂、PI3K抑制剂和SYK抑制剂等在不断研发中,其中,BTK抑制剂Ibrutinib、PI3K抑制剂Idelalisib和Duvelisib已获得批准用于临床,还有部分药物尚处于临床试验阶段。这些药物的毒性低,且在某些高危患者(如17P缺失等)中表现出较好的疗效。这些新型靶向药在CLL治疗中的地位越来越显著,并逐渐取代传统的化学免疫疗法。

Reaserch Advance on Inhibitor Targeting at the B-Cell Receptor Pathway in Chronic Lymphocytic Leukemia--Review

Objective:Disregulated BCR signaling pathway plays an important role in the occurence and progress of chronic lymphocytic leukemia(CLL).As key kinases of BCR pathway,the Bruton tyrosine kinase(BTK),phosphoinositide 3-kinase(PI3 K)and spleen tyrosine kinase(SYK)have become the focus of CLL targeted therapy.Over the past decade,drugs targeting of BCR pathway for CLL treatment have been continuously developed,including BTK inhibitors,PI3 K inhibitors and SYK inhibitors.To date,the BTK inhibitor Ibrutinib,PI3 K inhibitors Idelalisib and Duvelisib have been approved for CLL treatment,and some novel inhibitors are still in clinical trials.These targeted drugs are much less toxic than chemoimmunotherapy and show better efficacy in certain high-risk patients such as del 17 P.These inhibitors targeted BCR pathway are increasingly prominent in CLL treatment and gradually replace traditional chemoimmunotherapy.