Assessment of EGFR Modulation in HPV negative Head and Neck Cancer Cells and The effect on Response to Targeted Therapies


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Elham Alsahafi1,Mahvash Tavassoli1
1Kings College London

Abstract

Background

    The HPV negative head and neck cancers (HNSCC) have poor outcome due to the aggressive nature of the disease. Epidermal growth factor receptor (EGFR) regulates growth, survival and progression of HNSCCs representing a promising molecular target. Although, 90% of HNSCCs demonstrate overexpression of EGFR, the clinical response to EGFR inhibitors is only 10-15%. Cetuximab, an EGFR-targeted monoclonal antibody, has been approved clinically for advanced HNSCC treatment. There has been no direct correlation between EGFR overexpression and clinical response to cetuximab. This study aimed to assess the effects of EGFR modulation in HPV negative HNSCC cell lines and the response to cetuximab treatment.

Method

   HPV- HNSCC cell lines SCC-072 and UMSCC-22B, with low endogenous EGFR level were infected with EGFR-retroviral vector. The level of EGFR was assessed by western blot analysis. Functional characterisation of the modulated cell lines was performed by assessment of response to cetuximab, cellular proliferation/migration rate and direct immunofluorescence.

Results

   The EGFR modulation in both cell lines was successful. EGFR was overexpressed on the cell surface of both cell lines as noted by direct immunofluorescence. EGFR modulation resulted in increased cellular proliferation and migration rates. However, the modulated cell lines were not responsive to cetuximab.  

Conclusion

   The resistance of HPV- cell lines to cetuximab suggest that overexpression of EGFR may not be the only mechanism of response to the drug. The presence of other EGFR family members such as Her2, 3, 4 may influence the response. Additionally, studies are in progress to investigate the activation of other EGFR pathways. Effect of other EGFR inhibitors such as Gefitinib combined with radiotherapy is also being investigated. Notably, HPV+ HNSCCs have low EGFR expression compared to HPV- cancers and the former have favourable prognosis. Therefore, another aim of this study is to investigate whether EGFR is a factor in radiotherapy sensitivity in HPV+ HNSCCs.