Dual facets of copper in the malignant transformation of oral submucous fibrosis: A narrative review.

Copper is involved in the pathogenesis of oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC). The exact role of copper in the malignant transformation of OSMF remains unclear. This review aimed to highlight the role of copper in OSMF and its transformation to OSCC. A literature review was conducted in databases such as PubMed and Google Scholar to identify and analyse studies relevant to copper metabolism in OSMF and OSCC. Copper increases lysyl oxidase activity, leading to increased collagen cross-linking and extracellular matrix deposition, characteristic of OSMF. Studies indicate that excess copper induces oxidative stress, leading to epithelial injury and a microenvironment that favors malignant transformation. Furhter more, moderate elevations in intracellular copper concentrations have been associated with increased cellular proliferation, metabolic activity, and angiogenesis in OSCC. Direct evidence for copper-driven malignant transformation in OSMF remains limited. Copper appears to act as a context-dependent regulator, promoting fibrosis and tumor progression at moderate concentrations and being cytotoxic at higher concentrations. Understanding these copper-mediated biological mechanisms can provide a foundation for developing biomarkers to predict malignant riskosition in OSMF patients and for designing therapeutic strategies that modulate copper homeostasis.