Targeting Breast Cancer Vasculature
Abstract
The main problems with current cancer therapies, including those for breast cancer, are that they are only partially effective and highly toxic. We work on a strategy that enhances the efficacy of anti-tumor therapies, while simultaneously decreasing the side effects. Our target is the vasculature of tumors. Tumor cells depend on blood supply and the tumor vasculature is accessible through the blood stream. An added advantage is that the vasculature is composed of normal cell, which are unlikely to develop resistance to treatments. We identify tumor-specific vascular markers by screening phage-displayed peptide libraries in mice bearing breast cancer xenografts or endogenous transgenic breast cancers. When the libraries are intravenously injected into the mice, the phage that have specific affinity for tumor vasculature home to the tumors. These peptides can then be used to carry drugs and other therapeutics into tumors. The receptors for the peptides are potential drug targets. During the past year, the main findings are: (1) The discovery of a novel protein, which we have named metadherin, as a breast cancer cell surface protein that mediates the binding of the tumor cells to the lung vasculature, facilitating metastasis. (2) The identification of cell surface nucleolin as the receptor for a previously identified tumor-homing peptide, and (3) the as yet unpublished observation that antibodies to nucleolin have an anti-angiogenic activity in vitro and in vivo. These finding 5 ma lead to new ways 5 of combating metastasis and inhibiting tumor growth.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2004
- Accession Number
- ADA425815
Entities
People
- Erkki I. Ruoslahti
Organizations
- Sanford Burnham Prebys Medical Discovery Institute