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HER2/neu: a target for breast cancer therapy.

The receptor tyrosine kinase HER2 and its rat homologue neu were independently identified as close relatives of erbB, the gene encoding the epidermal growth factor receptor (EGFR). Genomic analysis of primary tumors revealed HER2 gene amplification and overexpression in breast and ovarian adenocarcinomas and demonstrated strong correlation with poor prognosis. Since its validation as the first human oncogene, HER2 has been intensively investigated as a target for therapeutic intervention. Nevertheless, it is still poorly understood how HER2 overexpression and enhanced cellular signaling contributes to the development of human cancer. Here we summarize the signaling characteristics of HER2 in regard to its function in tumorigenesis and address recent advances towards the pharmacological intervention in HER2 signaling and anti-cancer therapy.