布鲁顿氏酪氨酸激酶(BTK)抑制剂与难治性套细胞淋巴瘤  

Bruton tyrosine kinase inhibitors and refractory mantle cell lymphoma

作　　者：娄安琦 余俊先[2] 程子昭 苏强[1] LOU Anqi;YU Junxian;CHENG Zizhao;SU Qiang(Department of Oncology,Beijing Friendship Hospital,Capital Medical University,Beijing 10005,China;Department of Pharmacy,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China;School of Pharmacy Wenzhou Medical University,Wenzhou,Zhejiang 32503,China)

机构地区：[1]首都医科大学附属北京友谊医院肿瘤科,北京100050 [2]首都医科大学附属北京友谊医院药学部,北京100050 [3]温州医科大学药学院,浙江温州325035

出　　处：《中国临床药理学与治疗学》2021年第6期680-686,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：北京市教育委员会科技发展计划重点项目(KZ202010025047)。

摘　　要：布鲁顿氏酪氨酸激酶(Bruton tyrosine kinase,BTK)是B细胞受体信号转导的关键介体,也是套细胞淋巴瘤(mantle cell lymphoma,MCL)的临床有效治疗靶标。BTK抑制剂(bruton tyrosine kinase inhibitors,BTKI)在MCL治疗中发挥了关键作用,我们介绍了BTKI的作用机制。伊布替尼是第一代BTKI,临床疗效较好,但存在局限性,比如毒性和耐药问题。新型BTKI,如泽布替尼、阿卡替尼及奥布替尼,可以提高第一代BTKI的有效性和安全性。这篇综述比较了这两代BTKI在结构、功能上的异同,为BTKI更好地应用于临床提供依据。2019年11月15日,美国FDA批准泽布替尼上市,用于治疗经治的成年套细胞淋巴瘤患者。与伊布替尼相比,新一代BTKI泽布替尼靶点选择性更高,抑制更持久,不良反应少,患者受益更多。泽布替尼为复发/难治性MCL患者提供可行的治疗选择,同时也在积极开展治疗其他B细胞淋巴瘤的临床研究,是非常有前景的靶向药物。Bruton tyrosine kinase(BTK)is a key mediator of B-cell receptor signalling cascade and an effective target for treating mantle cell lymphoma(MCL).BTK inhibitors play a critical role in the treatment of MCL.Here we introduced the mechanism of action of BTKI in the treatment of MCL.Though generally well prescribed,Ibrutinib,as the first BTKI,still has limitations of toxicity and resistance.New BTK inhibitors,such as zanubrutinib,acalabrutinib and orelabrutinib,are designed to improve on the safety and efficacy as first-generation BTK inhibitors.Comparing the similarities and differences of the two generations of BTKI in structure and function provides a basis for better clinical application of BTKI.On November 15,2019,FDA approved zanubrutinib for marketing for patients with adult mantle cell lymphoma.Compared with Ibrutinib,zanubrutinib was found with higher target selectivity,longer-lasting inhibition,fewer adverse reactions,and better patient benefit.Zanubrutinib provides a viable treatment option for patients with r/r MCL.At the same time,it is also actively carrying out clinical researches on the treatment of other B-cell lymphomas.It is a very promising targeted drug.

关 键 词：布鲁顿氏酪氨酸激酶抑制剂 套细胞淋巴瘤 伊布替尼 泽布替尼 

分 类 号：R733[医药卫生—肿瘤]