Abstract
Cancer is the second leading cause of death in the United States and is currently on pace to become the leading cause by 2030 if the scientific and medical communities are unable to develop more effective diagnostic and treatment strategies. Advanced cancers continue to have high recurrence and low clinical response rates despite progress in cancer therapeutics. The mechanisms involved in tumor progression and metastasis often lead to drug resistance in cancer cells, rendering current treatment methods insufficient. Further complicating therapeutic mechanisms, tumors are heterogeneous populations of cells with different phenotypes and proliferative abilities. Thus, there is a need for novel therapeutic and diagnostic approaches that can efficiently target heterogeneous tumor populations in order to decrease tumor recurrence and metastasis, as well as improve our ability to diagnose patients. Targeting cancer stem cells (CSCs) could be a promising new strategy in cancer treatment and diagnosis. Although CSCs comprise a small percentage of the total tumor cell population, they have a significant role in metastasis, drug resistance, and tumor recurrence. Current therapies do not include specific tumor-targeting techniques and often have minimal effect on CSC populations. Chemotherapeutic drugs also affect normal cells, in addition to tumor cells, causing a wide-range of side effects that take a major toll on the body. Specific targeting of CSCs could reduce side effects and more effectively eradicate cancerous cells. Therefore, novel methods of drug delivery and early tumor detection should focus on CSCs. The aim of this project was to identify peptides that have high specificity for CSCs and other tumor cells. The One Bead One Compound (OBOC) method was used to develop peptides that bind specifically to αvβ6 integrin, which is overexpressed on both CSC and non-CSC tumor cells in a variety of cancers and is thus considered a strong tumor indicator. Therefore, we used a specific motif (R(G/T)DLXXL) found in proteins that bind αvβ6 integrin to build peptide libraries. Peptides were selected based on their ability to bind an αvβ6-expressing oral cancer cell line. Selected peptides were further examined using breast cancer cells and pancreatic cancer cells to explore their ability to bind various tumor cell types, including CSCs. Peptides identified in this study may ultimately be used in various clinical applications, including the delivery of chemotherapeutics and imaging probes to tumors. The delivery of chemotherapeutics and imaging probes can allow for noninvasive molecular imaging, earlier detection and more effective drug delivery.