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  • Title: Molecular pathways as novel therapeutic targets in systemic sclerosis.
    Author: Trojanowska M, Varga J.
    Journal: Curr Opin Rheumatol; 2007 Nov; 19(6):568-73. PubMed ID: 17917537.
    Abstract:
    PURPOSE OF REVIEW: Systemic sclerosis is a complex disease characterized by immune/inflammatory, vascular and fibrotic processes. To date, no treatment has proven effective in modifying the course of the disease. Recent studies have begun to yield insights into the nature and interrelationship among these processes, and their cellular and molecular components. RECENT FINDINGS: Novel intracellular molecular pathways have been characterized that positively or negatively regulate fibroblast responses contributing to the process of fibrosis. These include signaling mediators that specify and amplify transforming growth factor-beta responses, or inhibit collagen stimulation and block these responses in vitro and in animal models. Various gain of function or loss of function abnormalities in these mediators have been identified in systemic sclerosis, and may account for the characteristic activated phenotype of systemic sclerosis fibroblasts. SUMMARY: The identification of novel signaling pathways and mediators that are altered in systemic sclerosis and contribute to tissue damage allows their selective targeting. This in turn opens the door for novel therapeutic strategies utilizing novel compounds, or innovative ways of using already-approved drugs. In light of the complex pathogenesis of systemic sclerosis, however, only carefully designed clinical trials with appropriate biomarkers and outcome measures will be able to clarify the clinical utility of these innovative approaches.
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