Bruton's Tyrosine Kinase: Pathophysiological Roles and Inhibitor-Based Therapeutic Advances

Bruton's tyrosine kinase (BTK) plays a pivotal role in intracellular signaling within B-cells, governing development, differentiation, and survival, and is an integral target in treating B-cell malignancies and autoimmune disorders. The impact on B-cell receptor, Toll-like receptor, and chemokine receptor pathways establishes its therapeutic interest. This review integrates existing studies on BTK functional roles in immunology and BTK inhibitors (BTKis) targeting. Literature was ascertained by searching prominent databases such as PubMed, Embase, Web of Science and Google scholar for BTK's molecular biology, the history of BTKis and their clinical significance. The review addresses mechanisms of resistance, particularly the C481S mutation, which impedes covalent inhibition but is abrogated by non-covalent BTKis like pirtobrutinib, including BTK's application in autoimmune and inflammatory disorders, and discusses the importance of further long-term safety and efficacy in chronic diseases. BTK inhibitors have proven to be an essential part of targeted therapy for B-cell cancer, and continuing advances are addressing challenges like drug resistance and side effects. However, major challenges like the emergence of novel resistance mutations, the need for accurate biomarkers to direct therapy, and the continuing challenge of controlling drug-associated toxicities and maintaining costs under control still pertain. Ongoing research is essential to fully realize the therapeutic potential of BTK inhibitors and integrate them into personalized regimens for cancer and immune diseases alike.