This component will apply peptide library-based vascular targeting developed in the project leader's laboratory to profile molecular alterations in vasculature during prostate tumorigenesis. New peptides for both the blood vessel and lymphatic vasculature of prostate cancer will be isolated and their utility as tools for therapeutic targeting of prostate diseases will be explored. The design of the screening will favor peptides that generally recognize prostate cancer vasculature, rather than being selective for an individual prostate cancer model. The specificity of these peptides will be ascertained by testing peptide binding to normal and cancerous tissues from mice and from human patients. The target molecules ('receptors"""""""") for the most promising peptides will be identified and antibodies will be prepared against the receptors. The peptides identified and characterized as described above and antibodies prepared against their receptors will be tested for their effects on prostate cancer vasculature and tumor growth, and their ability to deliver peptide-drug or antibody-drug conjugates to pre-malignant prostate lesions and prostate cancers. Promising compounds emerging from these experiments will be tested in pre-clinical prostate cancer models for prevention and treatment of prostate cancer. New information on tissue- and tumor-specific vasculature specialization will be gained from this study. New therapies for preventing the development of prostate cancer and for treating established prostate cancer may emerge.
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