title: The Syk kinase as a therapeutic target in leukemia and lymphoma.
abstract: BACKGROUND
  The B-cell receptor (BCR) delivers antigen-dependent and -independent signals that have been implicated in the pathogenesis of several common B-cell malignancies. Agents that can efficiently block BCR signaling have recently been developed and are currently being evaluated as novel targeted therapies. Among these, agents that inhibit the Syk kinase appear particularly promising in preclinical and early clinical studies.
  
  
  METHODS
  The manuscript provides an overview of recent findings that implicate Syk and the BCR signaling pathway in the pathogenesis of several common lymphoid malignancies. It outlines preclinical and early clinical experiences with the Syk inhibitor fostamatinib disodium (R788) and discusses various options for further clinical development of this compound.
  
  
  CONCLUSIONS
  Inhibitors of Syk or other components of the BCR signaling pathway are emerging as an exciting novel class of agents for the treatment of common B-cell malignancies. Future efforts should focus on defining the disease entities that are most likely to benefit from these agents, although considerable evidence is already available to pursue such studies in patients with chronic lymphocytic leukemia. Combinations with chemo-immunotherapy, treatment of early-stage disease and consolidation therapy should all be explored and could lead to the development of novel therapeutic approaches with improved efficacy, tolerability and toxicity profiles.
authors: ICGEB -- Molecular Hematology, Campus “A. Buzzati-Traverso”, Rome, Italy. efremov@icgeb.org
authors: Dimitar G
authors: DG
authors: Efremov
authors: Luca
authors: L
authors: Laurenti
mesh_terms: D000631:Aminopyridines; D000818:Animals; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D007938:Leukemia / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008223:Lymphoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D058990:Molecular Targeted Therapy / Q000379:methods*; D009025:Morpholines; D010078:Oxazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000627:therapeutic use*; D011743:Pyrimidines; D000072377:Syk Kinase
chemical_list: D000631:Aminopyridines; D047908:Intracellular Signaling Peptides and Proteins; D009025:Morpholines; D010078:Oxazines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011743:Pyrimidines; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C523665:fostamatinib