Abstract
Epidermal growth factor receptor (EGFR) is a member of the ErbB family of receptors. Its stimulation by endogenous ligands, EGF or transforming growth factor-alpha (TGF-α) results in activation of intracellular tyrosine kinase, therefore, cell cycle progression. High levels of EGFR expression are correlated with poor prognosis and resistance to radiation therapy in a variety of cancers, mostly in squamous-cell carcinoma of the head and neck (SCCHN). Blocking the EGFR by a monoclonal antibody results in inhibition of the stimulation of the receptor, therefore, in inhibition of cell proliferation, enhanced apoptosis, and reduced angiogenesis, invasiveness and metastases. The EGFR is a prime target for new anticancer therapy in SCCHN, and other agents in development include small molecular tyrosine kinase inhibitors and antisense therapies.
Highlights
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 squamous-cell carcinoma of the head and neck (SCCHN) is still poor, with 5-year actuarial survival rates fluctuating between 30% and 40% in most trials [1]
High levels of Epidermal growth factor receptor (EGFR) expression are correlated with poor prognosis and resistance to radiation therapy in a variety of cancers, mostly in squamous-cell carcinoma of the head and neck (SCCHN)
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]
Summary
Despite decades of intensive clinical investigations, the outcome of patients presenting with stage III-IV HNSCC is still poor, with 5-year actuarial survival rates fluctuating between 30% and 40% in most trials These findings underscore the need to develop novel strategies in the management of patients with advanced HNSCC. The recent demonstration of a significant survival benefit when combining cetuximab with external RT is a major breakthrough in the management of SCCHN, establishing a new treatment option for locally advanced SCCHN. This trial provided an important proof of principle that targeting a pertinent signalling pathway can enhance the radiation response of tumors. ZD6474, a small molecule tyrosine kinase inhibitor of EGFR and VEGF, looks very promising for the future
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