title: B-cell receptor pathway modulators in NHL.
abstract: With the recent success of the Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, and the phosphoinositide-3-kinase (PI3K) inhibitor, idelalisib, in the treatment of patients with relapsed or refractory non-Hodgkin's lymphoma (NHL), a number of new agents targeting the B-cell receptor (BCR) pathway are in clinical development. In addition, multiple trials combining these agents with conventional cytotoxic chemotherapy, immunomodulatory agents, monoclonal antibodies, or other kinase inhibitors are underway. This review will summarize the current data with the use of single agent and combination therapy with BCR inhibitors in NHL. In addition, commonly encountered as well as serious toxicities and hypothesized resistance mechanisms will be discussed. Lastly, this review will examine the future of these agents and opportunities to maneuver them into the front-line setting in selected NHL subtypes.
authors.affiliation: Division of Hematology, The Ohio State University, Columbus, OH.
authors.forename: Kristie A
authors.initials: KA
authors.lastname: Blum
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D002986:Clinical Trials as Topic; D020869:Gene Expression Profiling; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008224:Lymphoma, Follicular / Q000276:immunology / Q000628:therapy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology / Q000628:therapy; D020522:Lymphoma, Mantle-Cell / Q000276:immunology / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000378:metabolism* / Q000628:therapy*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D064546:Protein Kinase C beta / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011687:Purines / Q000627:therapeutic use; D052999:Quinazolinones / Q000627:therapeutic use; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase; D008258:Waldenstrom Macroglobulinemia / Q000276:immunology / Q000628:therapy
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D011687:Purines; D052999:Quinazolinones; D011947:Receptors, Antigen, B-Cell; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000606896:SYK protein, human; D000072377:Syk Kinase; D064546:Protein Kinase C beta; C552946:idelalisib