The role of overexpressed HER2 in transformation.

The HER family of receptors has an important role in the network of cell signals controlling cell growth and differentiation. Although the activity of the HER receptor is strictly controlled in normal cells, HER2 receptor overexpression plays a pivotal role in transformation and tumorigenesis. HER2 gene amplification and/or overexpression of the receptor has been detected in subsets of a wide range of human cancers including breast cancer, and is an indicator of poor prognosis. It is proposed that overexpressed HER2 in combination with HER3 causes high activity of cell-signaling networks, thereby resulting in tumor cell proliferation. Thus, the HER2 receptor is an attractive target for new anti-cancer treatments. Monoclonal antibodies directed against the receptor are the most promising of these, and the humanized anti-HER2 monoclonal antibody trastuzumab (Herceptin) has shown significant clinical efficacy in clinical trials. The anti-tumor mechanisms of anti-HER2 monoclonal antibodies are not completely understood. However, some tumor types are not sensitive to trastuzumab, suggesting that the response of a tumor to trastuzumab may not only be dependent on overexpressed HER2, but may also be influenced by other members of the HER receptor family expressed in the tumor cell.