UC Riverside

Tumor heterogeneity poses a great challenge for current therapeutics. The ability of cancer cells to adapt and resist drug treatment provides a particular difficulty in two areas: having a full understanding of the mechanisms in which they adapt and a full understanding of how to overcome those mechanisms. Peptide-based therapeutics show great potential in confronting these challenges as they are known to aid in targeting drug targets previously deemed “undruggable.” To date, many peptide drugs are commercially available. With this in mind, our studies focused on the utilization of peptides for therapeutic purposes and investigating how cancer cell heterogenous characteristics respond to peptide drug treatment. In our first study, we treated cancer cells of known low mutational load with an immunogenic peptide. This treatment ultimately flagged the cancer cells as “pathogen-infected,” and we aimed to elicit an immune response. The second study incorporated a cyclic peptide into a proteolysis targeting chimera (PROTAC) structure to aid in the degradation of a commonly hyperactive protein in cancers known as AKT. This study also shed some light on the adaptation mechanisms cells can use in response to this drug treatment. In our final study, we used another cyclic peptide and other metabolic inhibitors to examine how varying types of inhibition affect the heterogeneity of cellular movement in cancer cells. Each study showcases how peptide-based drugs serve as a valuable tool for treating and further understanding the complexities of cancer.