) We have recently published a pilot study which describes the identification of cancer cells in the blood of 20 of 21 (95 percents) breast cancer patients before surgical excision of their primary tumor, even from patients with small tumors. The method gave no false positive results. These cancer cells in blood (CCIB) represent a novel and intrguing target for breast cancer therapeutics, as it is metastases that ultimately cause death. The main focus of the research in our laboratory is to identify small ligands which will home specifically to breast cancer cells and which can be used in the development of targeted therapeutics. We use phage-display random peptide library technology extensively and have identified small peptide ligands to several molecular targets relevant to breast cancer. In this proposal we describe the use of phage-displayed RPL technology to identify ligands to surface molecules located on cancer cells isolated from the blood of breast cancer patients. Pure populations of cancer cells will be isolated from the blood of breast cancer patients using a combination of immunomagnetic affmity selection methods and micropipeting assisted by laser optical trap manipulation. Once isolated, the CCIB will be screened with RPLs constructed in our laboratory. RPL screening with CCIB may elucidate novel peptides which bind specifically to the surface of cancer cells found in the blood of breast cancer patients. Such peptides can be conjugated to cytotoxic agents and hold great promise in the development of safe and effective breast cancer therapeutics.
