HER-2/neu-targeting gene therapy-a review

The HER-2/neu (also named c-erbB-2) oncogene is known to be overexpressed in many human cancers, including breast, ovarian, lung, gastric and oral cancers. In animal models, HER-2/neu overexpression was shown to enhance malignancy and metastasis phenotypes. Repression of HER-2/neu overexpression suppresses the malignant phenotypes of HER-2/neu-overexpressing cancer cells, suggesting that HER-2/neu may serve as an excellent target for developing anti-cancer agents. We have previously shown that the adenovirus-5 (Ad5) Ela 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 review, we summarize our recent findings on using cationic liposomes or an Ad vector to deliver Ela or large T into tumor-bearing mice. Our results indicate that both cationic liposomes or an Ad vector can efficiently deliver Ela or large T into tumor cells in mice, and this results in suppression of tumor growth and longer survival of the mice.