title: Targeting tyrosine kinases: a novel therapeutic strategy for systemic sclerosis.
abstract: OBJECTIVE
  This article reviews the current evidence and rationale for the use of tyrosine kinase inhibitors as potential therapeutic interventions for systemic sclerosis.
  
  
  RESULTS
  The signaling cascades of the profibrotic cytokines transforming growth factor-β and platelet-derived growth factor utilize tyrosine kinases. Preclinical studies have suggested potential efficacy of tyrosine kinase inhibitors in fibrosing disorders. Imatinib, dasatinib, and nilotinib treatment of scleroderma and normal fibroblasts leads to decreased production of extracellular matrix proteins in an in-vitro model. Several murine models demonstrate decreased skin thickening with tyrosine kinase inhibition. Case reports and one open-label trial suggest potential efficacy of imatinib in diffuse systemic sclerosis, although adverse events are common. One controlled and several uncontrolled trials are ongoing, and their results will better define the role of tyrosine kinase inhibition in the treatment of this disorder.
  
  
  CONCLUSIONS
  Tyrosine kinase inhibition as a potential strategy for the treatment of systemic sclerosis has been gaining more widespread interest based on preclinical data and open-label experiences. Large, multicenter, double-blind, randomized controlled trials are needed to assess the efficacy and safety of this approach in this complex disease.
authors.affiliation: Department of Rheumatology, Hospital for Special Surgery, New York 10021, USA.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Gordon
authors.forename: Robert F
authors.initials: RF
authors.lastname: Spiera
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis; D006801:Humans; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000502:physiology; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology
chemical_list: D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases