The epidermal growth factor receptor (EGFR) in head and neck cancer: its role and treatment implications

Squamous-cell carcinoma of the head and neck (SCCHN) remains a challenging clinical problem, due to the persisting high rate of local and distant failure, as well as the occurrence of second primaries. Treatment for early stage disease involves usually surgery and radiation therapy (RT). Locally-advanced tumors are best treated with concurrent chemotherapy to RT, either in the definitive setting or following surgery, according to each center's expertise.Although altered radiation fractionation and chemoradiotherapy had a favorable impact for advanced head and neck cancer patients, the outcome of patients presenting with stage III-IV SCCHN is still poor, with 5-year actuarial survival rates fluctuating between 30% and 40% in most trials [1].Recent research efforts have attempted to exploit biologic differences that may exist between normal and malignant cells, to develop tumor-specific therapies. The epidermal growth factor (EGF) and its receptor (EGFR, ErbB-1, or HER-1) were not only shown to play an influential role in cellular growth and differentiation in healthy tissues, but also in tumorigenesis and the progression of malignant disease [2].As well as being expressed on the surface of healthy cells, the EGFR is commonly expressed at high levels in a variety of epithelial tumors, including SCCHN. The aberrant activation of the EGFR leads to enhanced proliferation and other tumour-promoting activities, which provide a strong rationale to target this receptor.During the past decade, intense research has initiated a new era of cancer treatment, that of molecular therapeutics. Today, the EGFR is a prime target for new anticancer therapy, with a broad range of inhibitors currently under investigation [3].Promising preclinical studies have prompted the development of clinical trials testing EGFR inhibitors as single-agent therapy or in combination with conventional cytotoxic therapy, with response rates lower than anticipated in the advanced disease setting. The cleare