title: Inhibitors of B-cell receptor signaling for patients with B-cell malignancies.
abstract: The B-cell receptor (BCR) complex and its associated protein tyrosine kinases play a critical role in the development, proliferation, and survival of normal or malignant B cells. Regulated activity of the BCR complex promotes the expansion of selected B cells and the deletion of unwanted or self-reactive ones. Compounds that inhibit various components of this pathway, including spleen tyrosine kinase, Bruton's tyrosine kinase, and phosphoinositol-3 kinase, have been developed. We summarize the rationale for use of agents that can inhibit BCR signaling to treat patients with either indolent or aggressive B-cell lymphomas, highlight early clinical results, and speculate on the future application of such agents in the treatment of patients with various B-cell lymphomas.
authors.affiliation: UC San Diego Moores Cancer Center, La Jolla, CA 92093, USA.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Choi
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kipps
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000631:Aminopyridines; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009025:Morpholines; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010078:Oxazines / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010880:Piperidines; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011687:Purines / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D052999:Quinazolinones / Q000627:therapeutic use; D011947:Receptors, Antigen, B-Cell / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D000077157:Sorafenib
chemical_list: D000225:Adenine; D000631:Aminopyridines; D009025:Morpholines; D009536:Niacinamide; D010078:Oxazines; D010671:Phenylurea Compounds; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010880:Piperidines; D011505:Protein-Tyrosine Kinases; D011687:Purines; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; D052999:Quinazolinones; D011947:Receptors, Antigen, B-Cell; D000077157:Sorafenib; C551803:ibrutinib; C523665:fostamatinib; C552946:idelalisib