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HER-2/neu-targeting gene therapy--a review
1Department of Tumor Biology, M.D. Anderson Cancer Center, Houston 77030, USA.
Abstract:
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) 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 review, we summarize our recent findings on using cationic liposomes or an Ad vector to deliver E1a or large T into tumor-bearing mice. Our results indicate that both cationic liposomes or an Ad vector can efficiently deliver E1a or large T into tumor cells in mice, and this results in suppression of tumor growth and longer survival of the mice.
Insights
Gene therapy targeting the HER-2/neu oncogene shows promise for cancer treatment. Delivering E1a or large T genes using cationic liposomes or adenovirus vectors suppressed tumor growth and improved survival in mice.
Area of Science:
- Oncology
- Gene Therapy
- Molecular Biology
Background:
- HER-2/neu (c-erbB-2) oncogene overexpression is prevalent in various human cancers.
- HER-2/neu overexpression correlates with enhanced malignancy and metastasis.
- Targeting HER-2/neu is a promising strategy for anti-cancer agent development.
Purpose of the Study:
- To investigate the efficacy of delivering tumor suppressor genes (E1a or large T) into HER-2/neu-overexpressing tumors.
- To evaluate the potential of cationic liposomes and adenovirus (Ad) vectors for gene delivery in vivo.
- To assess the impact of gene delivery on tumor growth and animal survival.
Main Methods:
- Utilized cationic liposomes and Ad vectors for in vivo delivery of adenovirus-5 (Ad5) E1a gene products and SV40 large T antigen (large T).
- Administered gene therapies to tumor-bearing mice.
- Monitored tumor growth and animal survival rates.
Main Results:
- Both cationic liposomes and Ad vectors efficiently delivered E1a or large T into tumor cells in mice.
- Gene delivery resulted in significant suppression of tumor growth.
- Treated mice exhibited prolonged survival compared to controls.
Conclusions:
- Adenovirus-5 E1a and SV40 large T show potential in suppressing HER-2/neu-driven cancers.
- Cationic liposomes and Ad vectors are effective delivery systems for anti-cancer gene therapy.
- This approach offers a promising strategy for managing HER-2/neu-overexpressing tumors.