Targeting Bruton's Tyrosine Kinase Across B-Cell Malignancies.

Abstract:

: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.

journal_name

Drugs

journal_title

Drugs

authors

da Cunha-Bang C,Niemann CU

doi

10.1007/s40265-018-1003-6

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

1653-1663

issue

16

eissn

0012-6667

issn

1179-1950

pii

10.1007/s40265-018-1003-6

journal_volume

78

pub_type

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