Mara Sherman, PhD

Overview

In 2016, pancreatic cancer overtook breast cancer to become the third leading cause of cancer-related death in the United States. Therapies used to treat pancreatic cancer to date have provided limited benefit, suggesting that an improved understanding of complex mechanisms of disease progression is needed to develop effective therapeutic strategies. Pancreatic cancer is characterized in part by exuberant inflammation which infiltrates and surrounds the tumor, together known as the tumor microenvironment. The tumor microenvironment of pancreatic cancer both creates a harsh environment for cancer cells to grow, by limiting blood flow and nutrient availability within the tumor; and provides factors which enable cancer cells to grow and adapt in the context of this nutrient-poor, challenging microenvironment. I hypothesize that particular cells within the pancreatic tumor microenvironment known as stellate cells have evolved mechanisms to “feed” energy to cancer cells to simultaneously promote their survival and growth, and to regulate expression of cancer-supportive genes. To test this hypothesis, I will use a combination of patient-derived cancer and microenvironmental cells; these cell types will be cultured together to understand on a molecular level the impact of supportive cells on pancreatic cancer cell growth and behavior. These mechanistic studies will be accompanied by investigation of relevant metabolic pathways in mouse models of human pancreatic cancer, testing both genes and pharmacologic agents which may inhibit microenvironment-mediated tumor growth. Together, these studies have the potential to identify a novel metabolic liability of pancreatic cancer, which may be targetable for therapeutic benefit.