Phage display selection and evaluation of cancer drug targets.

Techniques for the construction of phage display libraries of combinatorial proteins have dramatically improved. This has allowed researchers to expand the applications to the field of cancer biology. The most direct use of protein phage-displayed libraries is the selection of ligands for individual proteins. This includes identification of peptide ligands for receptor signaling molecules: integrins, cytokine and growth factor receptors. Selected peptides may be used as competitors for natural ligands and for the mapping of binding epitopes. This approach has been exploited for delineation of intracellular signal transduction pathways and for the selection of enzyme substrates and inhibitors. Recently, more complicated biological systems were used as targets for biopanning. This includes combination of soluble proteins, cellular surfaces and even the vasculature of whole organs. cDNA expression libraries in phage-based vectors have been recently introduced. The use of phage as a vector for targeted gene therapy is also considered. These and other applications of phage display for cancer research will be reviewed.