PO-164 Modulation of EGFR to overcome tumour resistance and improve radiotherapy response in HPV positive and negative head and neck cancer cells

Introduction Squamous cell carcinoma of the head and neck (HNSCC) is a significant cause of morbidity and mortality, with over 6 00 000 new cases diagnosed annually. Development of targeted agents to improve survival and preserve organs is vital. This could be achieved through better understanding of the molecular status of HNSCC and availability of specific biomarkers to enable better detection, prognosis and prediction of treatment response. Epidermal growth factor receptor (EGFR) has a central role in HNSCC, causing excessive growth, survival and progression of cancer cells thus representing a promising molecular target for this disease. Over-expression of EGFR is detected in 80%–90% of HNSCC and correlates with worse disease outcome. More importantly, EGFR expression is lower in HPV positive HNSCC than HPV negative ones with the former demonstrating favourable prognosis. Moreover, hypoxia is a strong factor in solid tumours and is linked to more aggressive phenotype. Despite the development of anti-EGFR agents, limited clinical efficacy has been reported for EGFR inhibitors in HNSCC. In this study we assessed the effects of EGFR over-expression in relation to HPV status and further investigated the role of EGFR response to standard and targeted therapies. Additionally, we aim to understand the link between tumour hypoxia and EGFR signalling as well as the other ErbB family members in HNSCC cell lines. Material and methods HNSCC cell line SCC072 (HPV negative) and SCC154 (HPV positive) with low endogenous EGFR level were infected with EGFR-retroviral vector. The over-expression of EGFR was confirmed. Functional characterisation of both modulated cell lines was performed by assessment of cellular proliferation, migration, invasion and response to radiation/EGFR inhibitors. Additionally, EGFR activation and other ErbB family members were studied in both modulated cell lines. Results and discussions Modulation of EGFR in both cell lines showed variance in sub-cellular localisation. EGFR over-expression demonstrated oncogenic phynotype in both modulated cells. HPV- cells were resistance to targeted therapy, which suggest that EGFR over-expression may not be the only mechanism of response to targeted therapy. The presence of other EGFR family members may influence the response. Conclusion Studies are in progress to investigate EGFR pathways involved in invasion, metastasis and response to therapies. More importantly, is to consider the effect of tumour hypoxia on EGFR response to anti-cancer agents.