Curcumin as a potential new therapeutic approach against oral cancer

Head and neck cancer, the 8th most common cancer worldwide, is a heterogeneous disease that includes oral cancer. Oral cancer differs from other head and neck cancers both etiopathologically and prognostically. There is a significant difference in the incidence of oral cancer in various regions of the world, with age-adjusted rates varying from fewer than 2 per 100,000 individuals in the Middle East to 10 per 100,000 in the US, and to over 20 per 100,000 in India. Tongue cancer is the most frequent and the most aggressive among cancers of the oral cavity. It has been recently reported to be epidemic in the US due to a 4% annual increase rate, mainly in females younger than 44 years of age. Although molecular research has advanced remarkably during the last 40 years, the clinical outcomes of patients with oral cancer did not improve at the same pace, and 5- year survival rates remained ~50%. Moreover, 25% of patients with even small oral cancers that are treated with adequate surgery with clean margins and are expected to be cured proceed to develop local and/or local plus regional recurrence. Therefore, it seems that the current oncologic protocol aimed to destroy cancer cells, aggressive as it may be, is not sufficient enough, and this is because the disease remains in the surrounding microenvironment. Accordingly, numerous studies on the role of the tumor microenvironment(TME) in cancer growth, invasion and spread have been conducted during the last decade. Research on the TME of oral cancer has proved that the high density of cancerassociated fibroblasts, the development of hypoxic conditions, the recruitment of protumorigenic inflammatory cells and the changes in the extracellular matrix components are significantly correlated with poor prognosis. Thus, it is clearly mandatory to combat components of the TME. Administration of most of the currently developed anti-TME drugs is, however, expected to result in considerable toxic conditions among the oral cancer patients, making non-toxic nutraceuticals a desirable therapeutic option. Curcumin has proved to successfully combat both cancer cells and TME components in in-vitro studies and, as such, it emerges as being a preferred type of nutraceuticals. This chapter presents and discusses the mechanistic ways curcumin combats both oral cancer cells and the associated TME components. The low bioavailability of curcumin precludes its routine use in treating oral cancer, and new nanotechnologies for improving curcumin delivery will be presented.