Targeting TRP channels in oral cancer: Mechanistic potential and therapeutic promise

Oral cavity cancer remains a major clinical challenge due to its aggressive nature, rapid lymphatic spread, and limited therapeutic options. Despite advancements in diagnosis and treatment, patient prognosis continues to be poor, highlighting the urgent need for novel molecular targets. This review systematically examines the critical role of calcium (Ca²⁺) ion channels, particularly transient receptor potential (TRP) channels, in the initiation and progression of oral cancer. Comprehensive searches were conducted in Scopus, Embase, Web of Science, and Google Scholar databases up to January 2025. The focus centers on TRPA1, TRPV1-4, TRPM2, TRPM6, and TRPM8 channels, emphasizing their dysregulated expression, altered functionality, and downstream signaling in oral squamous cell carcinoma (OSCC). Emerging evidence demonstrates that aberrant TRP channel activity contributes to enhanced cell proliferation, migration, invasion, and survival, thereby promoting oral carcinogenesis. Additionally, the review explores the interplay between TRP-mediated calcium signaling and oncogenic pathways such as PI3K/AKT and MAPK, elucidating their collective impact on tumor behavior. By integrating insights from molecular biology, pharmacology, and clinical studies, this work underscores the therapeutic potential of targeting TRP channels as a novel approach in oral cancer management. Future research directions include delineating channel-protein interactions and developing selective TRP inhibitors to improve treatment outcomes.