Grant: Project Grant

Pancreatic cancer is the fourth leading cause of cancer-related deaths, primarily because the majority of patients have late stage disease when diagnosed. Three major types of precancerous lesions are associated with pancreatic ductal adenocarcinoma (PDAC) and increased detection of the large cystic versions of these precursor lesions in non-symptomatic patients via medical imaging modalities creates an opportunity to treat these patients and limit their disease progression. In order to provide targeted treatment to patients with these cystic lesions, we must better understand the cellular and molecular mechanisms underlying the initiation and progression of these lesions. We recently created a novel mouse model that spontaneously develops pancreatic cystic precursor lesions and recapitulates many aspects of human disease. Here, we propose to use this animal model to begin to understand how the immune response contributes to initiation and progression of intraductal papillary mucinous neoplasia, a subtype of cystic precancerous lesion associated with pancreatic cancer. These studies will shed light on the etiology of this subtype of lesion, identify a potential method to halt the progression of cystic precursors into invasive pancreatic cancer, and determine whether cancers associated with these lesions could be more responsive to immune modulatory therapies.