Inhibiting Bruton's Tyrosine Kinase in CLL and Other B-Cell Malignancies.

08:00 EDT 30th March 2019 | BioPortfolio

Summary of "Inhibiting Bruton's Tyrosine Kinase in CLL and Other B-Cell Malignancies."

Inhibitors of Bruton's tyrosine kinase (BTK), a major kinase in the B-cell receptor (BCR) signaling pathway, mediating B-cell proliferation and apoptosis, have substantially altered the management, clinical course, and outcome of patients with B-cell malignancies. This is especially true for patients with previously limited treatment options due to disease characteristics or coexisting diseases. Ibrutinib was the first orally available, nonselective and irreversible inhibitor of BTK approved for the treatment of patients with various B-cell malignancies. Newer and more selective BTK inhibitors are currently in clinical development, including acalabrutinib, which is currently US FDA approved for previously treated mantle cell lymphoma. Significant efforts are underway to investigate the optimal combinations, timing, and sequencing of BTK inhibitors with other regimens and targeted agents, and to capitalize on the immunomodulatory modes of action of BTK inhibitors to correct tumor-induced immune defects and to achieve long-lasting tumor control. This review describes the major milestones in the clinical development of BTK inhibitors in chronic lymphocytic leukemia and other B-cell malignancies, highlights the most recent long-term follow-up results, and evaluates the role of BTK inhibitors and their combination with other agents in B-cell malignancies and other indications.


Journal Details

This article was published in the following journal.

Name: Targeted oncology
ISSN: 1776-260X


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Medical and Biotech [MESH] Definitions

A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.

This enzyme is a lymphoid-specific src family tyrosine kinase that is critical for T-cell development and activation. Lck is associated with the cytoplasmic domains of CD4, CD8 and the beta-chain of the IL-2 receptor, and is thought to be involved in the earliest steps of TCR-mediated T-cell activation.

A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.

An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.

An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis.

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