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Epidermal Growth Factor Receptor Biology in Head and Neck Cancer

Shailaja Kalyankrishna, Jennifer R. Grandis

From the Departments of Otolaryngology and Pharmacology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA

Address reprint requests to Jennifer R. Grandis, MD, Department of Otolaryngology, The Eye and Ear Institute Building, Suite 500, 200 Lothrop St, Pittsburgh, PA 15213; e-mail: jgrandis{at}pitt.edu

Epidermal growth factor receptor (EGFR) is overexpressed in several epithelial malignancies, including head and neck squamous cell carcinoma (HNSCC), which exhibits EGFR overexpression in up to 90% of tumors. EGFR ligands such as transforming growth factor alpha are also overexpressed in HNSCC. EGFR plays a critical role in HNSCC growth, invasion, metastasis and angiogenesis. However, EGFR inhibitors as monotherapy have yielded only modest clinical outcomes. Potential mechanisms for lack of response to EGFR inhibition in HNSCC include constitutive activation of signaling pathways independent of EGFR, as well as genetic aberrations causing dysregulation of the cell cycle. EGFR-directed therapy may be optimized by identifying and selecting those HNSCC patients most likely to benefit from EGFR inhibition. Resistance to EGFR inhibition may be circumvented by combination therapy employing EGFR inhibitors together with other treatment modalities.

Supported by National Insitutes of Health (Bethesda, MD) Grant No. 1 P50 CA097190-01A1 (J.R.G.).

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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