Naturally-Occurring Bioactives in Oral Cancer: Preclinical and Clinical Studies, Bottlenecks and Future Directions.

Oral cancer (OC) is the eighth most common cancer, particularly prevalent in developing countries. Current treatment includes a multidisciplinary approach, involving chemo, radio, and immunotherapy and surgery, which depends on cancer stage and location. As a result of the side effects of currently available drugs, there has been an increasing interest in the search for naturally-occurring bioactives for treating all types of cancer, including OC. Thus, this comprehensive review aims to give a holistic view on OC incidence and impact, while highlights the preclinical and clinical studies related to the use of medicinal plants for OC prevention and the recent developments in bioactive synthetic analogs towards OC management. Chemoprophylactic therapies connect the use of natural and/or synthetic molecules to suppress, inhibit or revert the transformation of oral epithelial dysplasia (DOK) into oral squamous cell carcinoma (OSCC). Novel searches have underlined the promising role of plant extracts and phytochemical compounds, such as curcumin, green tea extract, resveratrol, isothiocyanates, lycopene or genistein against this malignancy. However, poor bioavailability and lack of in vivo and clinical studies and complex pharmacokinetic profiles limit their huge potential of application. However, recent nanotechnological and related advances have shown to be promising in improving the bioavailability, absorption and efficacy of such compounds.