Therapeutic Strategies in Epithelial Cancer Through Signalling Inhibition of the Epidermal Growth Factor Receptor.

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The growth of cancer cells is regulated by many factors, including the presence of growth receptors on the surface of cancer cells. The epidermal growth factor receptor (EGFR) is present in some normal tissues, but is highly expressed on many common cancers, including brain, breast, lung, head and neck, colon and prostate cancer. We are developing a number of potential therapeutic compounds that act by inhibiting the EGFR in cancer cells. These compounds include a novel monoclonal antibody that binds to EGFR and inhibits its function, and a small molecule that binds to a portion of the EGFR inside cancer cells and also inhibits function. Both of these compounds prevent tumour growth in laboratory studies. This project will examine the mechanisms of action of these compounds, and explore ways to improve their anti-cancer effect. We have also shown that combining these compounds with other therapeutics eg chemotherapy markedly enhances their anti-cancer effect. We will further examine the mechanisms of these effects, and also determine if radiotherapy has additive anti-cancer effects. These studies will provide a basis for improved therapies for cancers overexpressing the EGFR.