The biological roles and therapeutic potential of nicotinamide N-methyltransferase in ovarian cancer‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬.

Ovarian cancer (OC) continues to be a highly fatal gynecologic malignancy, primarily due to late-stage diagnosis, frequent recurrences, and the emergence of resistance to therapy. Nicotinamide N-methyltransferase (NNMT), a cytosolic metabolic enzyme, has been identified as a key regulator at the intersection of cellular metabolism and epigenetic remodeling. By methylating nicotinamide, NNMT influences NAD⁺ homeostasis, the SAM/SAH ratio, and histone methylation, which in turn affects energy metabolism, tumor-stroma interactions, and epigenetic plasticity. The excess expression of NNMT in ovarian cancer correlates with increased cancer cell expansion, stemness, epithelial-to-mesenchymal transition, and chemoresistance. Additionally, NNMT activity in cancer-associated fibroblasts, along with its metabolites, affects immune cell infiltration and tumor immunosuppression, thereby further facilitating tumor progression. Recent evidence also underscores the interaction between FTO (fat mass and obesity-associated)-mediated epitranscriptomic regulation and NNMT expression, connecting metabolic pathways and RNA methylation to therapeutic responses. In summary, these accomplishments demonstrate that NNMT is a viable therapeutic target in OC, suggesting potential strategies to counteract chemoresistance and enhance clinical outcomes.