| Abstract: |
The B cell receptor (BCR) signalling pathway has an integral role in the pathogenesis of many B cell malignancies, including chronic lymphocytic leukaemia, mantle cell lymphoma, diffuse large B cell lymphoma and Waldenström macroglobulinaemia. Bruton tyrosine kinase (BTK) is a key node mediating signal transduction downstream of the BCR. The advent of BTK inhibitors has revolutionized the treatment landscape of B cell malignancies, with these agents often replacing highly intensive and toxic chemoimmunotherapy regimens as the standard of care. In this Review, we discuss the pivotal trials that have led to the approval of various covalent BTK inhibitors, the current treatment indications for these agents and mechanisms of resistance. In addition, we discuss novel BTK-targeted therapies, including covalent, as well as non-covalent, BTK inhibitors, BTK degraders and combination doublet and triplet regimens, to provide insights on the best current treatment paradigms in the frontline setting and at disease relapse. © Springer Nature Limited 2024. |
| Keywords: |
signal transduction; treatment outcome; survival rate; clinical feature; review; cancer recurrence; drug efficacy; cancer staging; antineoplastic agent; mantle cell lymphoma; protein kinase inhibitor; antineoplastic combined chemotherapy protocols; waldenstroem macroglobulinemia; drug effect; drug resistance; drug resistance, neoplasm; risk factor; cancer resistance; protein kinase inhibitors; b cell lymphoma; lymphoma, b-cell; drug response; piperidines; clinical effectiveness; drug therapy; chronic lymphatic leukemia; follicular lymphoma; marginal zone lymphoma; leukemia, lymphocytic, chronic, b-cell; non-hodgkin lymphoma; adenine; molecularly targeted therapy; piperidine derivative; molecular targeted therapy; procedures; cancer prognosis; bruton tyrosine kinase; ibrutinib; humans; human; agammaglobulinaemia tyrosine kinase; b cell chronic lymphocytic leukemia; bruton tyrosine kinase inhibitor; pirtobrutinib; btk protein, human
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