BTK抑制剂在B细胞恶性肿瘤中的耐药性：机制和潜在的治疗策略。

IF 5.7 2区医学 Q1 HEMATOLOGY

Blood Reviews Pub Date : 2025-02-20 DOI:10.1016/j.blre.2025.101273

Xin Liu , Yufan Lin , Qiqi Zhuang , Haoren Deng , Aichun Liu , Jie Sun

{"title":"BTK抑制剂在B细胞恶性肿瘤中的耐药性：机制和潜在的治疗策略。","authors":"Xin Liu , Yufan Lin , Qiqi Zhuang , Haoren Deng , Aichun Liu , Jie Sun","doi":"10.1016/j.blre.2025.101273","DOIUrl":null,"url":null,"abstract":"<div><div>Bruton tyrosine kinase inhibitors (BTKi) have shown prominent clinical efficacy in patients with B cell malignancies, such as chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B cell lymphoma, and Waldenström's macroglobulinemia. Nevertheless, numerous factors contribute to BTKi resistance, encompassing genetic mutations, chromosomal aberrations, dysregulation of protein expression, tumor microenvironment, and metabolic reprogramming. Accordingly, potential therapeutic strategies have been explored to surmount BTKi resistance, including noncovalent BTKi, BTK proteolysis-targeting chimeras, and combination therapies. Herein, we summarize the mechanisms responsible for BTKi resistance as well as the current preclinical and clinical strategies to address BTKi resistance in B cell malignancies treatment.</div></div>","PeriodicalId":56139,"journal":{"name":"Blood Reviews","volume":"71 ","pages":"Article 101273"},"PeriodicalIF":5.7000,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"BTK inhibitors resistance in B cell malignancies: Mechanisms and potential therapeutic strategies\",\"authors\":\"Xin Liu , Yufan Lin , Qiqi Zhuang , Haoren Deng , Aichun Liu , Jie Sun\",\"doi\":\"10.1016/j.blre.2025.101273\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Bruton tyrosine kinase inhibitors (BTKi) have shown prominent clinical efficacy in patients with B cell malignancies, such as chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B cell lymphoma, and Waldenström's macroglobulinemia. Nevertheless, numerous factors contribute to BTKi resistance, encompassing genetic mutations, chromosomal aberrations, dysregulation of protein expression, tumor microenvironment, and metabolic reprogramming. Accordingly, potential therapeutic strategies have been explored to surmount BTKi resistance, including noncovalent BTKi, BTK proteolysis-targeting chimeras, and combination therapies. Herein, we summarize the mechanisms responsible for BTKi resistance as well as the current preclinical and clinical strategies to address BTKi resistance in B cell malignancies treatment.</div></div>\",\"PeriodicalId\":56139,\"journal\":{\"name\":\"Blood Reviews\",\"volume\":\"71 \",\"pages\":\"Article 101273\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2025-02-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Blood Reviews\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0268960X25000189\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Blood Reviews","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0268960X25000189","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

布鲁顿酪氨酸激酶抑制剂（Bruton tyrosine kinase inhibitors, BTKi）在慢性淋巴细胞白血病、套细胞淋巴瘤、弥漫性大B细胞淋巴瘤、Waldenström’s巨球蛋白血症等B细胞恶性肿瘤中表现出显著的临床疗效。然而，许多因素导致BTKi耐药，包括基因突变、染色体畸变、蛋白质表达失调、肿瘤微环境和代谢重编程。因此，研究人员探索了克服BTKi耐药性的潜在治疗策略，包括非共价BTKi、靶向BTK蛋白水解嵌合体和联合治疗。在此，我们总结了BTKi耐药的机制，以及目前在B细胞恶性肿瘤治疗中解决BTKi耐药的临床前和临床策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

BTK inhibitors resistance in B cell malignancies: Mechanisms and potential therapeutic strategies

查看原文本刊更多论文

BTK inhibitors resistance in B cell malignancies: Mechanisms and potential therapeutic strategies

Bruton tyrosine kinase inhibitors (BTKi) have shown prominent clinical efficacy in patients with B cell malignancies, such as chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B cell lymphoma, and Waldenström's macroglobulinemia. Nevertheless, numerous factors contribute to BTKi resistance, encompassing genetic mutations, chromosomal aberrations, dysregulation of protein expression, tumor microenvironment, and metabolic reprogramming. Accordingly, potential therapeutic strategies have been explored to surmount BTKi resistance, including noncovalent BTKi, BTK proteolysis-targeting chimeras, and combination therapies. Herein, we summarize the mechanisms responsible for BTKi resistance as well as the current preclinical and clinical strategies to address BTKi resistance in B cell malignancies treatment.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Blood Reviews 医学-血液学

CiteScore

13.80

自引率

1.40%

发文量

期刊介绍： Blood Reviews, a highly regarded international journal, serves as a vital information hub, offering comprehensive evaluations of clinical practices and research insights from esteemed experts. Specially commissioned, peer-reviewed articles authored by leading researchers and practitioners ensure extensive global coverage across all sub-specialties of hematology.