HER-2 NEU-TARGETING GENE-THERAPY - A REVIEW

The HER-2/neu (also named c-erbB-2) oncogene is known to be overexpres sed in many human cancers, including breast, ovarian, lung, gastric an d oral cancers. In animal models, HER-2/neu overexpression was shown t o enhance malignancy and metastasis phenotypes. Repression of HER-2/ne u overexpression suppresses the malignant phenotypes of HER-2/neu-over expressing cancer cells, suggesting that HER-2/neu may serve as an exc ellent target for developing anti-cancer agents. We have previously sh own that the adenovirus-5 (Ad5) E1a gene products and the SV40 large T antigen (large T) inhibit transcription of the HER-2/neu promoter and accordingly suppresses transformation induced by HER-2/neu. In this r eview, we summarize our recent findings on using cationic liposomes or an Ad vector to deliver E1a or large T into tumor-bearing mice. Our r esults indicate that both cationic liposomes or an Ad vector can effic iently deliver E1a or large T into tumor cells in mice, and this resul ts in suppression of tumor growth and longer survival of the mice.