**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** PANCREATIC CANCER IS OFTEN DIAGNOSED AT AN ADVANCED STAGE AND IT IS HIGHLY RESISTANT TO CONVENTIONAL CHEMOTHERAPY AND RADIATION THERAPY WHICH MAKES IT DIFFICULT TO TREAT. THE PROGRESSION FROM NORMAL PANCREATIC EPITHELIUM TO PANCREATIC CANCER IS ASSOCIATED WITH THE ACCUMULATION OF SEVERAL GENETIC MUTATIONS AND GRADUALLY EVOLVES VIA PRECURSOR LESIONS, CALLED PANCREATIC INTRAEPITHELIAL NEOPLASIA (PANIN) LESIONS. EPIDEMIOLOGICAL STUDIES HAVE SUGGESTED THAT CONSUMPTION OF CRUCIFEROUS VEGETABLES IS ASSOCIATED WITH A LOWER RISK OF DEVELOPING CANCERS, INCLUDING PANCREATIC CANCER.THE OVERARCHING GOAL OF THIS PROJECT IS TO CHARACTERIZE THE EFFICACY OF ORAL ADMINISTRATION OF THE CRUCIFEROUS VEGETABLE WATERCRESS (NASTURTIUM OFFICINALE) ON PREVENTING THE DEVELOPMENT AND PROGRESSION OF EARLY LESIONS OF PANCREATIC INTRAEPITHELIAL NEOPLASIA TO MORE ADVANCED LESIONS AND PANCREATIC CANCER, AND ON MODULATING THE GUT MICROBIOME. THE SPECIFIC AIMS OF THIS PROJECT ARE (1) TO DETERMINE THE EFFICACY OF FREEZE-DRIED WATERCRESS ON PREVENTING THE DEVELOPMENT AND PROGRESSION OF PRECURSOR PANIN LESIONS TO INVASIVE PANCREATIC ADENOCARCINOMA, BY USING A TRANSGENIC ANIMAL MODEL WHICH RESEMBLES HISTOPATHOLOGICAL FEATURES OF THE HUMAN DISEASE, AND (2) TO CHARACTERIZE THE EFFECT OF FREEZE-DRIED WATERCRESS CONSUMPTION ON THE GUT MICROBIOME USING METAGENOMICS SEQUENCING.THIS STUDY WILL PROVIDE INFORMATION REGARDING BIOMARKERS OF RESPONSE TO FREEZE-DRIED WATERCRESS IN A PANCREATIC CANCER MODEL. THE LONG-TERM GOAL IS TO DEVELOP A STRATEGY TO PREVENT THE PROGRESSION OF PANIN LESIONS TO PANCREATIC CANCER USING A WHOLE-FOOD APPROACH.