Curcumin-Based Adjuvant Strategies in Head and Neck Cancer: Synergistic Mechanisms and Translational Perspectives

Head and neck cancer (HNC) remains a major therapeutic challenge due to high recurrence rates, limited efficacy of current treatments, and the frequent emergence of therapeutic resistance. Curcumin and its analogs have gained increasing interest as adjuvant compounds capable of potentiating the efficacy of conventional anticancer strategies, including chemotherapy with cisplatin, paclitaxel, and 5-fluorouracil, as well as radiotherapy. This review summarizes preclinical and translational evidence investigating combination approaches involving curcumin-based compounds and standard therapies in HNC models, highlighting their synergistic effects on tumor growth inhibition, apoptosis induction, modulation of therapy resistance mechanisms, and mitigation of treatment-related toxicity. Strategies aimed at overcoming the pharmacokinetic limitations of curcumin, including nanoformulations, co-delivery systems, and targeted delivery platforms, are also discussed. By integrating current evidence, this review highlights the translational potential of curcumin and its analogs as adjuvant agents in multimodal HNC therapy, while identifying current gaps in clinical validation, and outlining future directions for improving therapeutic efficacy and safety.