mTOR Inhibition Strategies in Oropharyngeal Carcinoma

Oropharyngeal carcinoma (OPHC) belongs to the head and neck carcinoma (HNC) superfamily of malignant entities. Squamous cell carcinoma (SCC) represents the main histological type in them. Concerning the molecular substrate of OPHSCCs, imbalances in signal transduction pathways are implicated in their onset and progression. Among them, the phosphatidylinositol 3-kinase (PI3K)/tumor suppressor phosphatase and tensin homologue deleted on chromosome ten (PTEN)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway deregulation critically affects the clinico-pathological features and biological behavior of the corresponding malignancies. Especially, the mTOR oncogene (gene locus: 1p36.2) overactivation, due to point mutations and gene amplification, is a relatively frequent genetic event in OPHSCCs. For this reason, the molecule is a target for specific oncological therapeutic regimens. There is an increasing interest in developing and applying novel mTOR inhibitors in subsets of patients with the malignancy that demonstrate specific genetic signatures. In the current review, we focused on the mTOR gene and protein characteristics, their deregulation mechanisms in OPHSCCs and the conventional and novel agents that target and disrupt mTOR oncogenic activity in them.