3D Whole-Pancreas Analysis of Mouse Models of Pancreatic Cancer

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Project Summary This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA- 23-045 and is a collaboration between the Cellular Cancer Biology Imaging Research (CCBIR) Program and the Pancreatic Ductal Adenocarcinoma Stroma Reprogramming Consortium (PSRC). Pancreatic cancer is a deadly disease with a dismal prognosis but arises from precancerous lesions that lack the ability to spread beyond the pancreas, underscoring the opportunity for cancer interception in this disease. Genetically engineered mouse models provide a key opportunity to study premalignant pancreatic tumorigenesis over time to provide a rational foundation for such interception approaches, as serial tissue samples from these time points are not available from human patients. However, tools to quantify precancer burden in mice at the single-cell level through the whole pancreas are currently lacking; such tools would greatly improve the rigor of evaluation of these models. As such, we will leverage our recently developed deep learning tool CODA for 3D reconstruction and cellular quantification, which is undergoing expanded application and validation as part of the CCBIR Program. Using CODA, we will analyze whole pancreata from the inducible KRAS (iKRAS) mouse model, which allows assessment of epithelial-microenvironment cross talk at multiple time points in early tumorigenesis, a key goal of the PSRC. This collaboration between the CCBIR Program and the PSRC will apply novel cancer imaging technologies to innovative mouse models of pancreatic cancer, providing important insights into the cellular alterations in early pancreatic tumorigenesis. These studies will also provide additional validation of the CODA pipeline and poise this approach for application more broadly across mouse models of cancer.