Funded in memory of Patty Molloy.
Pancreatic cancer is one of the most lethal cancers and has a five-year survival rate of ~9%. This outcome is largely due to limitations in current diagnostic strategies as well a lack of eﬀective therapies. Thus, there is a dire need to better understand this disease. Recent studies in cancer research have indicated a causal relationship between the capacity of cancer cells to cope with stress and cancer progression and therapy resistance. Pancreatic tumors are driven by a gene called KRAS that is mutated in 95% of all human pancreatic cancers. We have recently found that one critical process driven by mutant KRAS is the formation of stress granules. Stress granules serve as a protective mechanism from chemotherapeutic agents, which kill cancer cells by inducing stress. In this proposal, my laboratory will determine the role of stress granules in the drug resistance of KRAS-driven pancreatic cancer, and develop strategies to block stress granules as a therapeutic tool. This approach has not been explored and could provide impactful insight for the treatment of this disease.