Role of BTK in B-cell Signaling and Disease
BTK is an essential element for B-cell receptor (BCR) signaling, which is required for B-cell maturation, survival, and proliferation. It is an upstream activator of multiple pro-survival/anti-apoptotic pathways, including the NF-KB, mTOR-AKT and ERK pathways. BTK is overexpressed in malignant cells from patients with various B-cell malignancies, such as chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). As demonstrated by the success of covalent BTK inhibitors approved by the FDA or in late-stage development, the inhibition of BTK is a validated strategy in these patient populations.