BTK inhibitors resistance in B cell malignancies: Mechanisms and potential therapeutic strategies
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Updated: Jul 3, 2026

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
Published on: December 7, 2014
Xin Liu1, Yufan Lin2, Qiqi Zhuang2
1Zhejiang Key Laboratory for Precision Diagnosis and Treatment of Hematological Malignancies, Hangzhou, China; Department of Hematology, Harbin Medical University Cancer Hospital, Harbin, China.
Abstract:
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.
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