Antiangiogenic Steroids and Growth Factor Receptors in Human Breast Cancer Therapy
Abstract
With 2,000,000 new cases worldwide annually, breast cancer is the most common malignancy in women. Genesis of these cancers depends, in part, on formation of a good blood supply, a process termed angiogenesis. Vascular endothelial growth factor (VEGF) stimulates growth of endothelial cells, and this critical protein is produced by breast cancers. High levels of VEGF secretion occur in tumors expressing EGF and HER-2 growth factor receptors. Anti-bodies to HER-2 receptor elicit direct anti tumor effects but also reduce VEGF secretion from tumors and, thereby, decrease angiogenesis. Optimal suppression of tumor growth may be achieved by combining anti-growth factor receptor therapies with agents that disrupt tumor angiogenesis, such as squalamine, a steroid that blocks VEGF-induced activity. This study probes the notion that treating both the tumor and the tumor-associated vasculature may be more effective than treating cancer cells alone. We are assessing specific binding and biologic activities of squalamine using vascular endothelial cells, with evidence for localization of squalamine in caveolae signaling domains. Moreover, we are evaluating the efficacy of squalamine alone and combined with other biologic agents, such as Herceptin and 204, in blocking growth and progression of human breast cancer xenografts in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2004
- Accession Number
- ADA431966
Entities
People
- Richard J. Pietras
Organizations
- University of California, Los Angeles