Retinoids as chemoprevention for head and neck cancer: where do we go from here?

The retinoids, natural and synthetic derivatives of vitamin A, have a promising role in the chemoprevention of head and neck squamous cell carcinoma despite facing the limitations of toxicity as well as innate and acquired resistance. Adhering to the concept of field cancerization and following multi-step carcinogenesis, premalignant lesions of the head and neck have long been the focus of intervention with retinoids. Similarly, these agents have been applied towards preventing second primary malignancies from developing following curative therapy for upper aerodigestive cancers. Despite encouraging response rates, the need for overcoming innate and acquired retinoid resistance as well as minimizing retinoid-related toxicity will likely be relegated to the new generation of receptor-selective, synthetic retinoids. In the interim, retinoid-non-retinoid combinations as well as other classes of chemopreventive agents seem to provide promise in curtailing the incidence of aerodigestive malignancies.