Mapping tumor vascular diversity by screening phage display libraries.

The structural and molecular diversity of tumor-associated vasculature provides a basis for the development of targeted diagnostics and therapeutics. Novel organ and disease-specific proteins expressed on tumor vasculature can be identified by in vivo phage display technology. Strategies for targeting tumor vessels should provide the advantages of selectivity of action plus improved accessibility and efficacy. The development of such targeting agents relies on the identification of specific ligand-receptor pairs and on information as to their cellular distribution and location. To date, the in vivo phage display screening system has allowed the selection of a variety of peptides targeting normal tissues, cancer and other angiogenesis-related diseases. Many receptors for these peptides have also been identified. In addition, complementary imaging studies are helping in the functional characterization of abnormalities occurring in blood vessels during tumor progression. These efforts will lead to the delineation of a ligand-receptor-based map of the microvasculature in human cancer. Several clinical applications may follow.