The "Guardian" Effect: Curcumin in Oral Premalignancy and Chemoprevention

Abstract

Oral potentially malignant disorders (OPMDs) form a heterogeneous group of lesions with a high potential for transformation to oral squamous cell carcinoma (OSCC). The concept of field cancerization describes the presence of genetically and epigenetically altered mucosa beyond the clinical boundaries of the lesion, contributing to the high rates of recurrence and second primary tumors. This necessitates the development of multi-targeted chemopreventive agents capable of addressing the entire field. Curcumin, a polyphenolic compound from *Curcuma longa*, has gained attention as a promising chemopreventive agent due to its pleiotropic effects. Curcumin targets the most important signaling pathways in the development of OSCC, such as NF-κB, STAT-3, and AP-1. In addition, it influences epigenetic changes, oxidative stress, and angiogenesis. In preclinical studies, curcumin has been shown to inhibit cell proliferation, induce apoptosis, and reverse epithelial-mesenchymal transition. In clinical settings, its potential in reducing the severity of the lesion and improving treatment outcomes has been demonstrated. In addition, its dual role as a radiosensitizer in tumor cells and a radioprotector in normal cells makes it more attractive. A comparative analysis of its safety profile and reduced recurrence rates compared to synthetic retinoids is also positive. However, its low bioavailability is a challenge. Advances in the formulation of nano- and mucoadhesive systems have been proposed to improve its bioavailability. This article aims to present the current evidence on the molecular basis of its action, its clinical application, and its therapeutic potential in the context of OPMD and field cancerization.