Sita Kugel, Ph.D.

Few words inspire more fear than “pancreatic cancer,” and for good reason. Pancreatic cancer is the third leading cause of cancer death in the United States and treatment regimens have changed little, despite these poor outcomes. Researchers have learned a great deal about the genetic mutations that give rise to pancreatic cancer. Yet, we still struggle to apply this information towards more effective treatments. An enormous challenge is that there are different “subtypes” of pancreatic cancer, which makes designing tailored treatments complicated. While studying individual pancreatic cancer subtypes, our lab identified a drug that can selectively kill the most lethal subtype of pancreatic cancer at extremely low doses. This subtype, referred to simply as QM, makes up ~25% of pancreatic tumors and has the worst overall prognosis of all subtypes. Further, because the drug works at such low doses, we may be able to treat patients at doses that do not cause significant toxicity. Here, we propose to define the details of how this drug kills QM pancreatic cancer cells. We will also test whether it can treat pancreatic cancer in mouse models. Finally, we will identify ways that cancer cells could develop resistance to this drug, a frustratingly common outcome. What we learn could help to develop modified versions of the drug or possible combination regimens to overcome resistance. The ultimate goal of our research is to identify new therapies that can be tested in clinical trials.