Targeting Treatment Resistance in Head and Neck Cancer through Unravelling Molecular Mechanisms

Head and neck cancer is a common malignancy worldwide and carries a poor prognosis when it is diagnosed late. Treatment itself often carries significant morbidity and impairs quality of life. There have been few actionable targets for squamous cell carcinoma of the head and neck, notably anti-epidermal growth factor receptor monoclonal antibody cetuximab and antiPD1 immunotherapy that have reached clinical use. We studied a polymorphism in the extracellular semaphorin domain of C-MET in the context of SCC head/neck and lung, uncovering a novel mechanism conferring biological aggressiveness and potential for therapeutic intervention. TP53 mutations are the most common somatic mutations in SCCHN and we studied the gain of function mutation p53R158G in the S4 strand of the DNA binding domain, uncovering the mechanism of carcinogenicity. In South East Asia including Malaysia and Singapore, nasopharyngeal carcinoma is associated with EBV and is the commonest head and neck malignancy, with a propensity for recurrence and metastases. We have interest in development of anti-vascular endothelial growth factor therapy as a means to overcome treatment resistance, and some of this work will be described in this presentation.