Imatinib and the Treatment of Fibrosis: Recent Trials and Tribulations

Overview

Journal Curr Rheumatol Rep

Publisher Current Science

Specialty Rheumatology

Date 2010 Nov 19

PMID 21086081

Citations 13

Authors

Jessica Gordon

Robert Spiera

Affiliations

Soon will be listed here.

Abstract

Imatinib mesylate has become a therapy of interest for the treatment of systemic sclerosis because of its ability to inhibit c-Abl and platelet-derived growth factor receptor, tyrosine kinases involved in profibrotic pathways. Preclinical data using in vitro and murine models of fibrosis have demonstrated the antifibrotic properties of imatinib. Imatinib is currently used widely in the treatment of chronic myelogenous leukemia, gastrointestinal stromal tumors, and other conditions, and a large amount of information is available regarding the safety of the medication in these patient populations. Whether imatinib will be tolerable or effective in the treatment of systemic sclerosis is the subject of several investigations. The aim of this review is to summarize this body of research to date.

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References

Chen Y, Leask A, Abraham D, Pala D, Shiwen X, Khan K . Heparan sulfate-dependent ERK activation contributes to the overexpression of fibrotic proteins and enhanced contraction by scleroderma fibroblasts. Arthritis Rheum. 2008; 58(2):577-85. DOI: 10.1002/art.23146. View

Hatano M, Yao A, Shiga T, Kinugawa K, Hirata Y, Nagai R . Imatinib mesylate has the potential to exert its efficacy by down-regulating the plasma concentration of platelet-derived growth factor in patients with pulmonary arterial hypertension. Int Heart J. 2010; 51(4):272-6. DOI: 10.1536/ihj.51.272. View

Wang S, Wilkes M, Leof E, Hirschberg R . Noncanonical TGF-beta pathways, mTORC1 and Abl, in renal interstitial fibrogenesis. Am J Physiol Renal Physiol. 2009; 298(1):F142-9. PMC: 2806113. DOI: 10.1152/ajprenal.00320.2009. View

Olivieri A, Locatelli F, Zecca M, Sanna A, Cimminiello M, Raimondi R . Imatinib for refractory chronic graft-versus-host disease with fibrotic features. Blood. 2009; 114(3):709-18. DOI: 10.1182/blood-2009-02-204156. View

Berman E, Nicolaides M, Maki R, Fleisher M, Chanel S, Scheu K . Altered bone and mineral metabolism in patients receiving imatinib mesylate. N Engl J Med. 2006; 354(19):2006-13. DOI: 10.1056/NEJMoa051140. View

Sfikakis P, Gorgoulis V, Katsiari C, Evangelou K, Kostopoulos C, Black C . Imatinib for the treatment of refractory, diffuse systemic sclerosis. Rheumatology (Oxford). 2008; 47(5):735-7. DOI: 10.1093/rheumatology/ken104. View

Bhattacharyya S, Ishida W, Wu M, Wilkes M, Mori Y, Hinchcliff M . A non-Smad mechanism of fibroblast activation by transforming growth factor-beta via c-Abl and Egr-1: selective modulation by imatinib mesylate. Oncogene. 2009; 28(10):1285-97. PMC: 4006376. DOI: 10.1038/onc.2008.479. View

Amjadi S, Maranian P, Furst D, Clements P, Wong W, Postlethwaite A . Course of the modified Rodnan skin thickness score in systemic sclerosis clinical trials: analysis of three large multicenter, double-blind, randomized controlled trials. Arthritis Rheum. 2009; 60(8):2490-8. PMC: 2725229. DOI: 10.1002/art.24681. View

Daniels C, Wilkes M, Edens M, Kottom T, Murphy S, Limper A . Imatinib mesylate inhibits the profibrogenic activity of TGF-beta and prevents bleomycin-mediated lung fibrosis. J Clin Invest. 2004; 114(9):1308-16. PMC: 524221. DOI: 10.1172/JCI19603. View

10.

Li M, Abdollahi A, Grone H, Lipson K, Belka C, Huber P . Late treatment with imatinib mesylate ameliorates radiation-induced lung fibrosis in a mouse model. Radiat Oncol. 2009; 4:66. PMC: 2802357. DOI: 10.1186/1748-717X-4-66. View

11.

Medsger Jr T . Natural history of systemic sclerosis and the assessment of disease activity, severity, functional status, and psychologic well-being. Rheum Dis Clin North Am. 2003; 29(2):255-73, vi. DOI: 10.1016/s0889-857x(03)00023-1. View

12.

Herrick A, Lunt M, Whidby N, Ennis H, Silman A, McHugh N . Observational study of treatment outcome in early diffuse cutaneous systemic sclerosis. J Rheumatol. 2009; 37(1):116-24. DOI: 10.3899/jrheum.090668. View

13.

Cohen M, Williams G, Johnson J, Duan J, Gobburu J, Rahman A . Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemia. Clin Cancer Res. 2002; 8(5):935-42. View

14.

Spiera R, Gordon J, Mersten J, Magro C, Mehta M, Wildman H . Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial. Ann Rheum Dis. 2011; 70(6):1003-9. PMC: 3086082. DOI: 10.1136/ard.2010.143974. View

15.

Sabnani I, Zucker M, Rosenstein E, Baran D, Arroyo L, Tsang P . A novel therapeutic approach to the treatment of scleroderma-associated pulmonary complications: safety and efficacy of combination therapy with imatinib and cyclophosphamide. Rheumatology (Oxford). 2008; 48(1):49-52. DOI: 10.1093/rheumatology/ken369. View

16.

Massague J, Seoane J, Wotton D . Smad transcription factors. Genes Dev. 2005; 19(23):2783-810. DOI: 10.1101/gad.1350705. View

17.

Clements P, Lachenbruch P, Seibold J, Zee B, Steen V, Brennan P . Skin thickness score in systemic sclerosis: an assessment of interobserver variability in 3 independent studies. J Rheumatol. 1993; 20(11):1892-6. View

18.

Dragun D, Distler J, Riemekasten G, Distler O . Stimulatory autoantibodies to platelet-derived growth factor receptors in systemic sclerosis: what functional autoimmunity could learn from receptor biology. Arthritis Rheum. 2009; 60(4):907-11. DOI: 10.1002/art.24364. View

19.

Svegliati Baroni S, Santillo M, Bevilacqua F, Luchetti M, Spadoni T, Mancini M . Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis. N Engl J Med. 2006; 354(25):2667-76. DOI: 10.1056/NEJMoa052955. View

20.

Tyndall A, Bannert B, Vonk M, Airo P, Cozzi F, Carreira P . Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis. 2010; 69(10):1809-15. DOI: 10.1136/ard.2009.114264. View