TAKING ADVANTAGE OF NOVEL VULNERABILITIES FOR THE TREATMENT OF PANCREATIC CANCER
A vast majority of pancreatic ductal adenocarcinomas (PDACs) have mutations in KRAS. This type of cancer is also notoriously difficult to treat, often resulting in patient death. Thus, there is a clear need to better understand PDAC progression. Here, I have discovered that the cell survival protein Survivin is highly upregulated in KRAS-driven pancreatic cancer cells and blocking Survivin expression using YM155 causes cell death. Moreover, treating PDAC cells with small doses of YM155 and the heat shock protein 90 (HSP90) inhibitor, Geldanamycin, was found to strongly kill certain PDAC cells, suggesting that drug combinations that include Survivin inhibition may hold promise as treatments for PDAC. Moreover, a YM155-resistant PDAC cell line was generated, which could be a powerful tool to investigate the mechanisms of drug resistance. These findings highlight Survivin as an important player in PDAC, and provide new insights regarding potential treatments for this disease.
Pancreatic Cancer; Survivin; YM155
Zax, David B.
Lancaster, Kyle M.
Chemistry and Chemical Biology
M.S., Chemistry and Chemical Biology
Master of Science
dissertation or thesis