Novel Therapeutic Approach for Breast Cancer
Abstract
Despite advances in the detection and treatment of breast cancer, the final impact on survival rates has not altered significantly. Based on these considerations, novel therapeutic approaches, such as gene-based therapy, offer promise for successfully treating this prevalent female disease. I am constructing replication competent bipartite adenoviruses (RCBA) in which the replication is controlled by the promoter of the PEG-3 gene (PEG-Prom) that shows cancer-selective activity and which simultaneously express either the cancer-selective apoptosis-inducing gene melanoma differentiation associated gene-7 (mda-7)/IL-24 or an immunomodulatory gene such as interferon-gamma or IL-2. I have demonstrated that PEA-3 and AP-l, transcription factors involved in regulating oncogenesis and tumor progression, are involved in the regulation of PEG-prom activity in breast cancer cells. I have also demonstrated that RCBA in which replication is controlled by PEG-Prom and which expresses mda-7/IL-24 (Ad.PEG-ElA.CMV-mda-7) kills breast cancer cells without harming normal breast epithelial cells. However, RCBA in which replication is controlled by CMV promoter (Ad.CMV-ElA.CMV- mda-7) kills both breast cancer and normal cells indicating the breast cancer-selective killing property of Ad.PEG-ElA.CMV-mda-7. This exciting initial observation indicates that Ad.PEG-ElA.CMV-mda-7 might be a valuable tool for actual therapeutic application in patients with breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2004
- Accession Number
- ADA428427
Entities
People
- Devanand Sarkar
Organizations
- Columbia University