Sita Kugel, PhD

Few words inspire more fear than “pancreatic cancer,” which is the third leading cause of cancer death in the United States. Treatments have changed little over recent years despite the fact that researchers have learned a great deal about the genetic mutations that give rise to pancreatic cancer. One challenge is that there are different “subtypes” of pancreatic cancer, thereby making a one-size fits all approach difficult. Tailored therapeutic approaches are desperately needed. While studying pancreatic cancer subtypes, our lab identified that drugs which block a protein called cyclin-dependent kinase 7 (CDK7) could selectively kill the most lethal subtype of pancreatic cancer at extremely low doses. This subtype, referred to simply as basal, makes up ~25% of pancreatic tumors and has the worst overall survival. 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 study a drug that inhibits CDK7, in patients with early-stage pancreatic cancer following chemotherapy and before surgery. Concurrently, we will test new pancreatic cancer treatment strategies and drug combinations in mouse models of pancreatic cancer. We will validate and search for new blood markers of treatment response and drug resistance. Finally, we will identify pathways that allow cancer cells to survive CDK7 inhibition and determine whether other drugs can be added to enhance this therapy. The ultimate goal of our research is to provide a new targeted treatment option and hope to pancreatic cancer patients.