Targeting Bruton's tyrosine kinase in B cell malignancies

Bruton's tyrosine kinase (BTK) is important in B cell receptor (BCR) signalling, and so BTK is altered in many types of B cell-derived malignancy. This Review discusses the molecular biology of BTK, its involvement in the pathogenesis of B cell malignancies and the current efforts to therapeutically target it. Bruton's tyrosine kinase (BTK) is a key component of B cell receptor (BCR) signalling and functions as an important regulator of cell proliferation and cell survival in various B cell malignancies. Small-molecule inhibitors of BTK have shown antitumour activity in animal models and, recently, in clinical studies. High response rates were reported in patients with chronic lymphocytic leukaemia and mantle cell lymphoma. Remarkably, BTK inhibitors have molecular effects that cannot be explained by the classic role of BTK in BCR signalling. In this Review, we highlight the importance of BTK in various signalling pathways in the context of its therapeutic inhibition.