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Are tyrosine kinase inhibitors promising for the treatment of systemic sclerosis and other fibrotic diseases?


Beyer, C; Distler, J H W; Distler, O (2010). Are tyrosine kinase inhibitors promising for the treatment of systemic sclerosis and other fibrotic diseases? Swiss Medical Weekly, 140:w13050.

Abstract

Tissue fibrosis causes organ failure and death in patients with systemic sclerosis (SSc), but clearly effective anti-fibrotic therapies are not available. The tyrosine kinase inhibitor (TKI) imatinib, which blocks the pro-fibrotic c-Abl kinase and PDGF receptor, is currently evaluated in clinical proof-of-concept trials for the treatment of patients with SSc. In experimental models, imatinib efficiently prevented and reduced tissue fibrosis. First clinical case studies demonstrated anti-fibrotic effects of imatinib in selected patients with SSc and other fibrotic diseases, and observational studies in sclerotic chronic graft-versus-host disease showed promising results. Besides imatinib, the two novel TKIs of c-Abl and PDGF receptor nilotinib and dasatinib have recently proven efficacy in experimental models of SSc. The potential of TKIs of the VEGF receptor (e.g., semaxinib, vatalanib, sutent, and sorafenib) and the EGF receptor (e.g., erlotinib, gefitinib, lapatinib, and canertinib) as anti-fibrotic treatments are also discussed in this review. Prior to clinical use, however, controlled trials need to address efficacy as well as tolerability of TKIs in patients with different fibrotic diseases.

Tissue fibrosis causes organ failure and death in patients with systemic sclerosis (SSc), but clearly effective anti-fibrotic therapies are not available. The tyrosine kinase inhibitor (TKI) imatinib, which blocks the pro-fibrotic c-Abl kinase and PDGF receptor, is currently evaluated in clinical proof-of-concept trials for the treatment of patients with SSc. In experimental models, imatinib efficiently prevented and reduced tissue fibrosis. First clinical case studies demonstrated anti-fibrotic effects of imatinib in selected patients with SSc and other fibrotic diseases, and observational studies in sclerotic chronic graft-versus-host disease showed promising results. Besides imatinib, the two novel TKIs of c-Abl and PDGF receptor nilotinib and dasatinib have recently proven efficacy in experimental models of SSc. The potential of TKIs of the VEGF receptor (e.g., semaxinib, vatalanib, sutent, and sorafenib) and the EGF receptor (e.g., erlotinib, gefitinib, lapatinib, and canertinib) as anti-fibrotic treatments are also discussed in this review. Prior to clinical use, however, controlled trials need to address efficacy as well as tolerability of TKIs in patients with different fibrotic diseases.

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10 citations in Web of Science®
2 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2010
Deposited On:01 Feb 2011 14:05
Last Modified:05 Apr 2016 14:40
Publisher:EMH Swiss Medical Publishers
ISSN:0036-7672
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:10.4414/smw.2010.13050
PubMed ID:20419513
Permanent URL: http://doi.org/10.5167/uzh-43812

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