A potential role for imatinib and other small molecule tyrosine kinase inhibitors in the treatment of systemic and localized sclerosis.
Small molecule tyrosine kinase (TK) inhibitor, such as imatinib, is well established in the treatment of malignancy. Oral administration, high efficacy, and an excellent safety profile have made imatinib a drug of choice for several malignancies and benign conditions. Recent progress in the understanding of several benign conditions has led to the use of TK inhibitors in the treatment of hypereosinophilic syndrome and mastocytosis. Systemic sclerosis (SS) is a recalcitrant disease featuring multiorgan fibrosis and dysfunction. Molecular and biological evidence point to a central role for platelet-derived growth factor receptor, a TK-associated entity, in the pathogenesis of SS. The ability of several TK inhibitors, namely imatinib, to abrogate the activation of platelet-derived growth factor receptor-TK may entail their use in the treatment of SS and possibly more limited forms of sclerosis. Several human studies aiming to examine the use of imatinib in the treatment of SS are currently underway.
Bibi
Yuval
Y
Department of Dermatology at Boston University School of Medicine, Boston, Massachusetts 02118, USA. yuvalbn@yahoo.com
Gottlieb
Alice B
AB
D001549:Benzamides; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011928:Raynaud Disease / Q000209:etiology / Q000517:prevention & control; D012594:Scleroderma, Localized / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D012595:Scleroderma, Systemic / Q000188:drug therapy*; D012867:Skin / Q000473:pathology
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate