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Pancreatic cancer develops through a series of precursor lesions known as Pancreatic Intraepithelial Neoplasia or PanINs. PanINs are characterized by the presence of a mutated form of the Kras gene and, in advanced lesions, by loss of tumor suppressor genes. Cell signaling pathways that are important during embryonic development but are normally inactive in most adult cells are reactivated in PanINs and in pancreatic cancer.

The Pasca di Magliano laboratory uses genetically engineered mouse models to study the initiation, progression and maintenance of Pancreatic adenocarcinoma.  Lab members work on several projects related to pancreatic cancer:

  • Cancer Maintenance: The goal of this project is to determine which oncogenes or signaling pathways are important for the maintenance of metastatic adenocarcinoma. We have recently demonstrated that continuous expression of oncogenic Kras is required for cancer maintenance. Now, we are investigating which downstream effectors of Kras are important for cancer maintenance, and thus potential targets for therapy.

  • Inflammation and Pancreatic Cancer: The formation of pancreatic cancer is accompanied by the formation of an inflammatory microenvironment. We are investigating both cellular components and signaling molecules (cytokines) to determine how the inflammatory microenvironmnet contributes to pancreatic cancer initiation and progression.

  • Epithelial-Mesenchymal Interactions in Pancreatic Cancer: Pancreatic cancer is characterized by extensive accumulation of desmoplastic stroma. The goal of this project is to characterize the origin and nature of the different components of the stroma, and to understand their contribution to the process of tumorigenesis.

    Regression of early stages of pancreatic cancer following Kras* inactivation. Precursor lesions are caught reprogramming from ductal-like structures (CK19 - green) into normal pancreatic acinar cells (amylase - red). Cells that co-express both markers, CK19 on the membrane and amylase in the cytoplasm, are in the process of transdifferentiation.