Advancing BTK Inhibition: Non‑Covalent Bruton Tyrosine Kinase Inhibitors and Their Emerging Role in Canadian Practice

Authors

  • Jonathan Isenberg, MD Division of Medical Oncology, Centre for Lymphoid Cancer, University of British Columbia and BC Cancer, Vancouver, BC
  • Alina S. Gerrie, MD, MPH, FRCPC Division of Medical Oncology, Centre for Lymphoid Cancer, University of British Columbia and BC Cancer, Vancouver, BC, University of British Columbia, Centre for Lymphoid Cancer, BC Cancer

DOI:

https://doi.org/10.58931/cht.2025.4s0469

Abstract

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. 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.

Author Biographies

Jonathan Isenberg, MD, Division of Medical Oncology, Centre for Lymphoid Cancer, University of British Columbia and BC Cancer, Vancouver, BC

Dr. Jonathan Isenberg is a hematologist and internist currently completing a clinical fellowship in lymphoma and myeloma at BC Cancer in Vancouver, Canada. He earned his medical degree from the Hebrew University of Jerusalem and served as a military physician prior to completing his residency in internal medicine and a fellowship in hematology-oncology at Rambam Health Care Campus in Haifa, Israel. His main clinical and research interests focus on lymphoma and multiple myeloma, with a particular emphasis on novel therapies and cellular treatments.

Alina S. Gerrie, MD, MPH, FRCPC, Division of Medical Oncology, Centre for Lymphoid Cancer, University of British Columbia and BC Cancer, Vancouver, BC, University of British Columbia, Centre for Lymphoid Cancer, BC Cancer

Dr. Alina Gerrie is a hematologist and Associate Professor in the Divisions of Medical Oncology and Hematology at the University of British Columbia (UBC) and a Clinician Investigator at the Centre for Lymphoid Cancer at BC Cancer, Vancouver Centre. She completed her medical degree and internal medicine residency at the University of Toronto, followed by hematology residency at UBC. She undertook a fellowship through the Royal College Clinical Investigator Program and earned a Master of Public Health degree from Harvard University, where her research included investigating the impact of genetic abnormalities on population-level outcomes in chronic lymphocytic leukemia (CLL) patients. Dr. Gerrie currently holds a Michael Smith Health Research Investigator Award and is involved in translational, clinical trial and outcomes-based research related to leukemia and lymphoma. Other academic interests include the investigation of novel therapeutics and cellular therapy for CLL and lymphoma.

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2025-06-27

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Isenberg J, Gerrie AS. Advancing BTK Inhibition: Non‑Covalent Bruton Tyrosine Kinase Inhibitors and Their Emerging Role in Canadian Practice. Can Hematol Today [Internet]. 2025 Jun. 27 [cited 2025 Jun. 29];4(s04):2–15. Available from: https://canadianhematologytoday.com/article/view/4-s04-Isenberg_et_al

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