The growing significance of human epidermal growth factor receptor 2 (HER2) as therapeutic treatment target in head and neck cancer

Attenuation of the cell surface receptor (epidermal growth factor receptor, EGFR) mediated signaling cascade is a proven effective treatment approach in treating epithelial malignancies. The receptor tyrosine kinase (RTK) could be activated by a number of growth factors reversibly such as EGF, TGF-alpha, heregulins and HB-EGF. Inhibition of the activation of the EGFR receptor will block the activation of significant oncogenic signaling cascades including phosphatidylinositol-3-kinase (PI3K)/AKT pathway, mitogen-activated protein kinase (MAPK) pathway and JAK-STAT signaling pathway. Aberrations of the EGFR family are frequently observed in head and neck cancer. Specific genotypes will affect the treatment outcome and hence impact the prognosis of cancer patients. The use of EGFR tyrosine kinase inhibitors or specific antibodies is proven to be useful. However, the effects will gradually decline with the development of resistant phenotype. Recent data suggest that cancer cells will compensate the loss of EGFR-mediated signaling effects by increasing the signaling output of other EGFR members such as HER2. Human HER2 (ERBB2 or NEU) is one of the 4 members of the EGFR family. Gene amplification and protein overexpression of HER2 are found in head and neck cancer. Histological data revealed that protein overexpression of HER2 is site- specific with particular high frequency observed in a subset of cancers in head and neck regions. This chapter will provide a summary on HER2 with particular focus on the therapeutic aspects. Further, the significance of HER2 and the growing recognition of the particular functional roles in head and neck cancers will be addressed.