title: Emerging protein kinase inhibitors for the treatment of non-Hodgkin's lymphoma.
abstract: BACKGROUND
  non-Hodgkin's lymphoma (NHL) accounts for 4.3% of all new cancers in the United States. Even in its most curable subtypes, approximately 30% of patients succumb to their disease. For these patients there is clear need for more effective therapy. In indolent NHL where survival is prolonged, the aim of therapy is improving quality of life and limiting the burden of therapy.
  
  
  METHODS
  The key signaling mechanisms of normal B-cells, the changes that are seen in signaling in NHL, and the targets of novel protein kinase inhibitors (PKIs) are discussed. The efficacy of these agents in both aggressive and indolent histologies is reviewed. Logical combinations of novel and traditional agents are explored. Ongoing studies of the new agents are discussed.
  
  
  CONCLUSIONS
  PKIs will likely modify standard therapeutic paradigms in NHL. As use of these agents increases and combination studies continue, optimal use will depend on individual disease characteristics, goals of therapy as well as patient and societal costs. Future clinical trials need to be designed with appropriate end points given prolonged use in many cases of these orally administered, well tolerated compounds. Further, safeguards against cumulative and/or unique side effects need to be in place given the novel signaling pathways being targeted.
authors: University of Rochester Medical Center , Rochester, NY , USA paul_barr@urmc.rochester.edu.
authors: Sudy
authors: S
authors: Jahangiri
authors: Jonathan
authors: J
authors: Friedberg
authors: Paul
authors: P
authors: Barr
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011788:Quality of Life; D015398:Signal Transduction / Q000187:drug effects; D013534:Survival
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors
keywords: B-cell receptor; ibrutinib; idelalisib; non-Hodgkin lymphoma; protein kinase inhibitor