Prevention of the Angiogenic Switch in Human Breast Cancer
Abstract
Our studies over the past 5 years have focused on investigating the mechanisms that regulate the angiogenic switch in primary breast cancers and progression towards metastasis, as well as development of novel therapies that target these processes. While it is well accepted that initiation of cancer requires activation of an oncogene and/or loss of tumor suppressors, tumor progression to neoplasia and subsequent tumor mass expansion require activation of the angiogenic switch (1). To determine the mechanisms that regulate the angiogenic switch, we utilized multiple approaches including screens to identify genes that may be causal in triggering this switch, investigation of the role of the breast cancer susceptibility gene (BRCA1) in regulating angiogenic proteins, and identifying soluble factors produced by non-metastatic breast cancer cells that are critical in suppressing the growth of metastatic lesions. To examine the efficacy of novel therapies for breast cancer with anti-angiogenic activity, we focused on two specific anti-angiogenic therapies, a novel oral formulation of the fumagillin analogue TNP-470 called Lodamin and a recombinant peptide consisting of the first 27 amino acids in the endogenous angiogenesis inhibitor endostatin. We evaluated the efficacy of these two novel anti-angiogenic agents on the growth of human breast cancer in immunocompromised mice and confirmed their primary mechanism of action. The results from these studies have advanced our understanding of how the angiogenic switch may be regulated in breast cancer and provide insight into novel targets and signaling pathways for both primary breast tumorigenesis and more advanced metastatic disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2009
- Accession Number
- ADA542543
Entities
People
- Donald E. Ingber