Targeting Bruton’s Tyrosine Kinase Across B-Cell Malignancies
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Bruton’s tyrosine kinase (BTK) is crucial in B-cell development and survival. The role of BTK as a downstream kinase in the B-cell receptor (BCR) signaling pathway is well described. As a key player in the pathogenesis of B-cell malignancies, targeting of dysregulated BCR signaling has been explored by development of inhibitors of downstream mediators. Discovery of the biological function of BTK and the development of covalent inhibitors for clinical use, ibrutinib as the lead agent and acalabrutinib as the second clinically approved BTK inhibitor, have revolutionized the treatment options for B-cell malignancies. Currently, ibrutinib is approved for mantle cell lymphoma, chronic lymphocytic leukemia, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, small lymphocytic lymphoma, marginal zone lymphoma and chronic graft versus host disease, while acalabrutinib is approved for mantle cell lymphoma. Potential expansion of indications in other diseases is under investigation in several clinical trials, while combination of BTK inhibitors with either chemoimmunotherapy or other targeted agents is being systematically explored in B-cell malignancies.
Compliance with Ethical Standards
This study was funded by The Danish Cancer Society (Grant number R-130-A8217-15-S38) and The Novo Nordisk Foundation (Grant number NNF16OC0019302).
Conflict of interest
Carsten Utoft Niemann has received grants from Janssen and Abbvie; consulting fees from Roche, Gilead, Janssen, Abbvie, AstraZeneca, and CSL Behring; and travel support to meetings from Roche, Gilead, Janssen, and Abbvie. Caspar da Cunha-Bang declares no conflicts of interest that might be relevant to the contents of this article.
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