Oral squamous cell carcinoma (OSCC) is the most common malignancy of the head and neck region. OSCC patients are usually diagnosed with advanced disease and have a low five-year survival rate of 45% that is compounded due to late detection. The major risk factors for OSCC are tobacco use, alcohol abuse, genetic predisposition and infection with human papilloma viruses (HPV). Historical reports have indicated that the integrity of the superficial layer of the oral epithelium, forming the outermost protective barrier, is chronically impacted by exposure to the major risk factors, leading to cancer pre-disposition. However, defining the key effectors of barrier impairment and oral homeostasis is a totally unexplored area due to the lack of relevant animal models, with no significant insights in the literature regarding the molecular mechanisms that potentially link them.
Our laboratory has recently generated mouse models of OSCC using the risk factors affecting humans. Those models are currently being examined and quantified for the spatial and temporal oral integrity properties. Strikingly, our preliminary data indicate that postnatal disruption of the oral barrier function induces spontaneous OSCC that is accelerated in the presence of chemical carcinogens, providing the first mechanistic insight into the role of compromised barrier function in the development of OSCC.
In summary, this research is identifying the cellular and molecular mechanisms by which compromised barrier integrity induces OSCC. The outcomes are expected to present novel therapeutic opportunities for patients who, either due to exposure history, premalignant lesions, or a prior diagnosis of OSCC, are at high risk of succumbing to this fatal malignancy for which there is currently no approved preventative therapy.