Background: Oral submucous fibrosis is an oral potentially malignant disorder with high
incidence of malignant transformation and rising global prevalence. However, the genesis of oral submucous
fibrosis is still unclear despite superfluity of literature. In the background of ineffective treatment,
it is necessary to decode its onset and progression before designing customized treatment regimens.
Objective: The objective of this article is to decipher the pathogenesis of oral submucous fibrosis in
order to identify novel drug targets.
Methods: A thorough literature review based on oral submucous fibrosis being an overhealing wound
was conducted; several related patents were identified and herewith reviewed. Necessary pathways
were elaborated and deliberated in the manuscript in the form of schemas, keeping our hypothesis in
mind. Several novel molecular targets were identified and discussed in detail.
Results: Several patents demonstrating inhibition of fibrosis via chemokine ligand mimetics, anticonnexon
antibodies, stem cell therapy, fibronectin blocking peptides, HIF inhibitors, recombinant
erythropoietin, xanthine oxidase inhibitors, long non-coding RNAs, targeting inflammation, increasing
TH-1/TH-2 cytokine ratio, t-box protein 4, chromium containing compositions, Iron-based nanocomposites,
Lactate Dehydrogenase-5 inhibitors, Carbonic Anhdrase-9 inhibitors, proton pump inhibitors,
liposomal encapsulated glutathione, monocarboxylate-4 inhibitors, autophagy inhibitors, Submucosal
anti-IL-6 antibodies, fibrin degradation products for monitoring of malignancy and fibrosis, small
molecule antagonists like vorapaxar, tiplaxtinin, and TM-5275, TGF-β signalling inhibitors were identified
as future therapeutic avenues.
Conclusion: Considering, oral submucous fibrosis as an overhealing wound explains both pathogenesis
and malignant transformation. Certainly, abnormalities in coagulation and fibrinolytic system are a
common denominator in the profibrotic milieu and associated malignancy.