HER2 overexpression and cancer targeting.

Overexpression of the HER2/neu oncogene is a frequent molecular event in multiple human cancers including breast and ovarian cancer. Patients with breast cancer that overexpress HER2/neu have a poor prognosis, shorter relapse time, and low survival rate. In this report, the biologic signaling pathway mediated by HER2/neu tyrosine kinase receptor will be discussed. The mechanisms leading to transformation and tumorigenesis of HER2/neu-overexpressing cells will also be addressed. Treatments that target HER2/neu expression in cancer cells have been shown to be useful strategies to significantly reverse the malignancy induced by HER2/neu overexpression. In this report we will summarize strategies for targeting the HER2/neu gene, including targeting the gene product p185 oncoprotein, or transcriptional downregulation through the oncogene promoter. These fundamental studies, performed by different groups, warrant the clinical potential of targeting HER2/neu in cancer therapy. Copyright 2001 by W.B. Saunders Company.