Targeting IKK in Basal-Like Breast Tumors as a Therapeutic Approach
Abstract
Specifically, our hypothesis is that IKK and a form of NF-kB are activated in certain breast tumors (including the majority of basal-like tumors), leading to the expression of genes which promote oncogenesis and which lead to resistance to therapy. Additionally, we hypothesize that these tumors will respond to inhibitors of this pathway, either alone or in combination with chemotherapy. Based on our findings, we hypothesize that IKK/NF-kB and Bcl2A1 (a key gene regulated by NF-kB that is found upregulated in basal-like breast cancer) are key determinants of cancer therapy resistance in certain breast tumors. Our aims are to: (i) Generate a tumor bank archive for the analysis of NF-kB/IKK activation and associated gene expression, and correlate the findings derived from this analysis to breast tumor subtypes, (ii) Determine the mechanism of activation of Bcl2A1 and other NF-kB-dependent genes in basal-like cells; identify signaling components required for NF-kB activation in basal-like cancer cells; examine inhibitors of the NF-kB/IKK pathway in vitro, and (iii) Characterize animal models of breast cancer for activation of NF-kB and for potential therapeutic responses to NF-kB inhibitors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2009
- Accession Number
- ADA513452
Entities
People
- Albert S Baldwin
Organizations
- University of North Carolina at Chapel Hill