Project 466984

Head and neck cancer is the 6th most common cancer in the world. It typically arises in the lining of the mouth, neck, and throat and is collectively referred to as head and neck squamous cell carcinoma (HNSCC). Recently, infection by the sexually transmitted disease human papillomavirus has drastically increased HNSCC diagnoses, especially in the younger population. HPV-driven (HPV+) HNSCC has consequently been coined a slow epidemic posing a particular risk for patients resistant to chemotherapy and radiation who are at higher risk of mortality. Additionally, chemoradiation treatment has associated toxicities such as difficulties swallowing, pain, and hearing loss. Currently, biomarkers related to treatment resistance in HPV+ HNSCC have not yet been identified to explain the portion of patients who respond negatively to treatment. To address these concerns, our lab has identified candidate genes that may play a pivotal role in conferring treatment resistance in HPV+ HNSCC. A gene of interest, mono-ADP ribosylhydrolase 2 (MACROD2) has been named a novel tumour suppressor gene in related cancers and is associated with enhanced cell proliferation and tumour recurrence. In this study, the biological role of MACROD2 will be validated through functional assays in HPV+ HNSCC cell lines. Thereafter, mouse models will be evaluated for the growth of HPV+ HNSCC tumours. Through this work, the molecular basis of treatment resistance in HPV+ HNSCC can be better understood allowing low-risk patients to undergo less intensive treatments ; decreasing their associated toxicities ; and high-risk patients to undergo enhanced treatment. As a result, our findings can provide a framework for enhancing the therapeutic efficacy of chemoradiation in HPV+ HNSCC and related malignancies.