A potential role for imatinib and other small molecule tyrosine kinase inhibitors in the treatment of systemic and localized sclerosis.

Abstract

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.