Diagnostic & targeting reagents for lung cancer

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Lung cancer is the largest cancer killer of both men and women in the United States. Discoveryof ligands specific to receptor(s) on a surface of a lung cancer cell will impact clinical issues including functional diagnosis andcell-specific drug delivery. Our overall goal is to generate a panel of cell- specific molecules that couldbe used to classify tumor types and then be exploited for targeted delivery of therapeutics. Using phage display technologies, my laboratory has developed platform methodologies to isolate peptides that bind to and mediate uptake into specific cells. We have successfully identified cell-specific targeting peptides for 30 different cell types, including 7 cancer cell lines. The isolated peptides display remarkable cell-specificities, even among similar cells, and are able to discriminate between normal and cancerous cells as well as different lung tumor cells. This high discriminating power suggests that peptides could be identified that selectively bind to differenttumor types, even those with similar classifications. We propose to isolate cell-targeting peptides for 16 different lung cancer lines and then utilize these peptides as diagnostic and tumor specific delivery reagents. These peptides will be assayed for affinity and cell-specificity. Efforts will be directed towards translating the targeting phage into small molecule targeting reagents and these peptide scaffoldswill be utilized to deliver therapeutics to tumor cells both in vitro and in vivo. The cell specificity demonstrated by these peptides indicates that they are recognizing distinct cell surface receptors that may be of clinical value as biomarkers for lung cancer. Thus, we will utilize the peptides to identify the cellular these unique cellular features. We will then explore the expression patterns of the receptor on a panel of human lung cancer tissues by immunohistochemistry and compare this with the expression level in matched normal tissues. Achieving our goals will impact lung cancer diagnosis and treatment as well as solving general challenges in the field of targeted drug delivery.