Targets of BCR signaling. Signaling through the B-cell receptor (BCR) leads to activation of multiple downstream kinases and is critical for cell survival. Agents are in early and late clinical development targeting key components of the cascade, including Bruton tyrosine kinase (BTK), PI3K, SYK, mammalian target of rapamycin (MTOR), and AKT appear promising with activity observed across B-cell malignancies. CK indicates cytokine; TLR, toll-like receptor; Ca, calcium; PIP3, phosphatidylinositol triphosphase; and PIP2, phosphatidylinositol biphosphate.