Synergistic Inhibition of Her2/neu and p53-MDM2 Pathways. Addendum
Abstract
Overexpression of HER2/neu, as well as the overexpression of MDM2 has been known to be significant markers in malignancy of breast cancer in different ways. Activating the p53 pathway (a tumor suppressor protein) by inhibiting MDM2 activity while inactivating HER2/neu (a tumor activating protein) is a unique strategy to restore both wild type p53 function and inhibit poor breast cancer cell receptor function. Therefore, combination of drugs targeting HER2/neu and MDM2 pathways will allow for a two-pronged attack on breast cancer. The overall objective of our proposal is to determine if small molecule drugs designed to inhibit HER2/neu can be applied in combination with drugs designed to inhibit p53-MDM2 activity. This will enable us to ascertain if there is a synergistic effect as well as allow us to develop an understanding of the critical players in the overall cell signaling cascade. Initially, our objectives will be to design novel therapeutic agents based on pharmacophore and docking studies able to inhibit either the HER2/neu pathway or the p53-MDM2 pathway. Subsequently, designed small molecule drugs able to strongly induce apoptosis in breast cancer cell lines by inhibiting either pathway will be used in combination studies in vitro and in vivo to assess synergistic effects.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2007
- Accession Number
- ADA519805
Entities
People
- Nouri Neamati
Organizations
- University of Southern California