Abstract: Head and Neck Cancer (HNC) represents a significant global health challenge, marked by high incidence, poor prognosis, and frequent association with chronic inflammation. Pain management in HNC is complex and often inadequate. Curcumin and resveratrol, two naturally occurring polyphenols, have attracted considerable attention for their anti-inflammatory and anti-cancer activities. This review systematically examines the molecular mechanisms by which curcumin and resveratrol modulate key signaling pathways, including NF-κB, STAT3, PI3K/Akt/mTOR, and SIRT1, in the context of HNC progression and pain. Curcumin exerts its effects by inhibiting pro-inflammatory cytokines, suppressing tumor proliferation, and inducing apoptosis, while resveratrol activates SIRT1, inhibits MAPK and mTOR pathways, and enhances apoptosis and anti-metastatic effects. Both compounds influence the tumor microenvironment, potentially enhancing anti-tumor immunity. Combined, they may provide synergistic benefits, including augmented apoptosis and enhanced modulation of inflammatory pathways. Preclinical evidence supports their efficacy in tumor suppression and pain reduction, though clinical translation remains limited due to poor bioavailability. Recent advances in nanoformulations have improved systemic delivery, and initial clinical trials show promising effects in reducing oral mucositis and modulating antioxidant status. However, large, well-designed clinical trials are needed to confirm their therapeutic roles, clarify synergistic mechanisms, and optimize formulations for effective HNC treatment. Dedicated research on pain management and opioid-sparing effects is especially warranted. Together, curcumin and resveratrol represent promising adjuncts to current HNC therapies, with the potential to improve tumor control and patient quality of life.
Lu et al. (Mon,) studied this question.