Tyrosine kinase inhibitor therapy for systemic sclerosis: Quo Vadis?

Mendoza, Fabian A.; Jiménez, Sergio A.

doi:10.1002/art.30545

Cited by 7 publications

(1 citation statement)

References 45 publications

(56 reference statements)

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“…A number of exploratory translational studies from plasma and skin biopsies were reported as not changing significantly from 0 to 6 months other than sVCAM in plasma and sICAM-1 in skin, but data were not provided. An editorial pointed out that these inclusion criteria were somewhat unusual as well as the issue with using this medication in patients with myopathy [ 49 ]. This trial allowed concomitant use of methotrexate, which can have pharmacologic interaction with imatinib [ 50 ].…”

Section: Introductionmentioning

confidence: 99%

Tyrosine Kinase Inhibitors in the Treatment of Systemic Sclerosis: The Difficulty in Interpreting Proof-of-Concept Studies

Gordon

Spiera

2011

International Journal of Rheumatology

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Tyrosine kinase inhibitors (TKIs) have emerged as a targeted therapy of interest for the treatment of systemic sclerosis (SSc). Recently, several groups have performed pilot or “proof-of-concept” studies to determine the feasibility of this approach for the treatment of the cutaneous and pulmonary manifestations of this multisystem disease. The conclusions drawn by these different studies have been conflicting, and some controversy has arisen as to whether tyrosine kinase inhibition is a treatment approach worthy of continued study. This paper summarizes this research to date with emphasis on the challenges in interpreting proof-of-concept studies in this patient group.

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Section: Introductionmentioning

confidence: 99%

Tyrosine Kinase Inhibitors in the Treatment of Systemic Sclerosis: The Difficulty in Interpreting Proof-of-Concept Studies

Gordon

Spiera

2011

International Journal of Rheumatology

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Tyrosine kinase signaling in fibrotic disorders

Beyer

Distler

2013

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

105

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Tyrosine kinases regulate a broad variety of physiological cell processes, including metabolism, growth, differentiation and apoptosis. Abnormal tyrosine kinase activity disturbs the physiological cell homeostasis and can lead to cancer, vascular disease, and fibrosis. In regard to fibrosis, different tyrosine kinases have been identified as determinants of disease progression and potential targets for anti-fibrotic therapies. This includes both receptor tyrosine kinases (e.g., PDGF receptor, VEGF receptor, EGF receptor, and JAK kinases) as well as non-receptor tyrosine kinases (e.g., c-Abl, c-Kit, and Src kinases). Given their central role in the pathogenesis of fibrosis, researchers of our field study the anti-fibrotic effects of monoclonal antibodies or small-molecule inhibitors to block the aberrant tyrosine kinase activity and treat fibrosis in preclinical models of various fibrotic diseases (e.g., idiopathic pulmonary fibrosis, renal fibrosis, liver fibrosis, and dermal fibrosis). The results of these studies were promising and prompted clinical trials with different compounds in fibrotic diseases. So far, results from studies with intedanib in idiopathic pulmonary fibrosis and imatinib in idiopathic pulmonary fibrosis and systemic sclerosis have been reported. Although none of these studies reported a positive primary outcome, promising trends in anti-fibrotic efficacy awaken our hopes for a new class of effective anti-fibrotic targeted therapies. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease.

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