https://canadianhematologytoday.com/issue/feedCanadian Hematology Today2025-06-27T15:40:22+00:00Open Journal Systemshttps://canadianhematologytoday.com/article/view/4-s04-Isenberg_et_alAdvancing BTK Inhibition: Non‑Covalent Bruton Tyrosine Kinase Inhibitors and Their Emerging Role in Canadian Practice2025-06-27T15:40:22+00:00Jonathan IsenbergAlina S. Gerrie<p class="p1">The B-cell receptor (BCR) signaling pathway is a key driver in the development of B-cell malignancies, such as chronic lymphocytic leukemia (CLL), Waldenstrom’s macroglobulinemia (WM), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL), by promoting abnormal proliferation and survival. Antigen binding to the BCR triggers activation of Bruton’s tyrosine kinase (BTK), which in turn leads to activation of the nuclear factor kappa-B (NFκB) pathway, leading to nuclear translocation of NF-κB transcription factors.<span class="Apple-converted-space"> </span>The essential role of BTK activation in BCR signaling highlights the rationale for BTK inhibition as a targeted therapeutic intervention in B-cell malignancies, effectively suppressing BCR signaling and limiting B-cell proliferation and survival.</p>2025-06-27T00:00:00+00:00Copyright (c) 2025 Canadian Hematology Today