Abstract
Oral submucous fibrosis (OSMF) is considered a premalignant condition characterized by aggressive fibrosis of the submucosal tissues of the oral cavity reflecting its malignant transformation potential. Activation of transforming growth factor beta (TGF-β) signaling has been reported to lead increased collagen production and fibrosis. Recently, significant upregulation of TGF-β1 has been reported in OSMF as compared to normal tissues. Therefore, inhibition of the TGF-β1 may pave for the development of therapeutics of OSMF. Based on the structure-assisted drug designing, we found “silmitasertib” as potent inhibitor of TGF-β1. We suggest that this molecule can be validated and implemented for the treatment of OSMF.
Highlights
Oral submucous fibrosis (OSMF) is considered a premalignant condition characterized by aggressive fibrosis of the submucosal tissues of the oral cavity reflecting its malignant transformation potential [1]
Findings support the premise that this promising small molecule can be validated and implemented for the treatment of OSMF
It has been reported that upregulated TGF-β1 signaling in epithelial cells affects the nearby fibroblasts leading canonical downstream SMAD signaling activation that results in mesenchymal interaction leading to fibrosis [10,11,12,13,14]
Summary
Oral submucous fibrosis (OSMF) is considered a premalignant condition characterized by aggressive fibrosis of the submucosal tissues of the oral cavity reflecting its malignant transformation potential [1]. Submucosal fibrosis usually affects oral cavity, pharynx, and esophagus leading to dysphagia and progressive trismus and increases the risk for development of cancer [2]. Activation of transforming growth factor beta (TGF-β) signaling has been reported to lead increased collagen production, and fibrosis and significant upregulation of TGF-β1 have been reported in OSMF as compared to normal tissues [3]. Epidemiological evidences reflect exponential increase in OSMF in younger male population [6]. Studies indicated that near about 10% OSMF cases are associated with malignant transformation to oral squamous cell carcinoma (OSCC) [7, 8]
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