BTK

OVERVIEW1

Bruton’s tyrosine kinase (BTK) is a signaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways. BTK’s role in signaling through the B-cell surface receptors results in activation of pathways necessary for B-cell trafficking, chemotaxis, and adhesion. 


IMPLICATIONS IN CANCER2

BTK is critical for oncogenic signaling in multiple B-cell malignancies including mantle cell lymphoma (MCL), follicular lymphoma (FL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and Waldenström’s macroglobulinemia (WM). Malignant B cell survival, proliferation, and interactions with the tumor microenvironment require BTK.  In MCL, BTK is essential for retention of cancer cells in lymphoid tissues.  Constitutively active pathways essential for CLL survival require BTK. Phosphorylated BTK triggers NF-kb signaling in WM leading to survival and proliferation and BTK mediated NF-kb signaling is known to play an important role in FL as well.

  1. Dobrovolsky D, et al. Bruton Tyrosine Kinase Degradation as a Therapeutic Strategy for Cancer. Blood. 2019;133(9):952-961.
  2. Singh P, et al. Role of Bruton’s tyrosine kinase in B cells and malignancies. Mol Cancer. 2018;17(57).