Animal Modeling of Pancreatitis-to-Cancer Progression

  • Paola Martinelli
  • Francisco X. Real
Reference work entry


Inflammatory diseases are the most common conditions of the exocrine pancreas. Chronic pancreatitis is often the result of recurrent bouts of acute pancreatitis and is a risk factor for pancreatic cancer. There has been a long interest in modeling the pathophysiological relationship between chronic pancreatitis and cancer and the recent development of genetic mouse models of pancreatic diseases has accelerated the discovery of mechanistic insights. The current paradigm proposes that the inability of normal pancreatic cells to recover from injury establishes a biological landscape that promotes cancer development. Multiple types of mechanisms concur in this process, in which both epithelial and nonepithelial cells participate, leading to persistent inability of epithelial cells to restore their differentiation programs. Developmental pathways involved in pancreatic differentiation are subverted to maintain cellular phenotypes that promote signaling from mutant KRAS, preneoplasia, and neoplasia. Downstream from KRAS, and in parallel with it, tyrosine kinase receptors, the MAPK, PI3K, NF-KB, and STAT pathways, and the mechanisms that control senescence and autophagy, contribute to the emergence of transformed clones. These signaling pathways, whose activity is modulated through complex cross-talks between epithelial, mesenchymal, and inflammatory cells, play crucial roles in the pancreatitis-to-cancer progression and provide opportunities for intervention in high-risk patients.


Pancreatitis Pancreatic cancer Caerulein Acino-ductal metaplasia 

List of Abbreviations


Acinar-to-ductal metaplasia


Acute pancreatitis




CCK receptor


Choline-deficient, ethionine-supplemented diet


Cystic fibrosis transmembrane conductance regulator


Chronic pancreatitis


Extracellular matrix


Epidermal growth factor


Endoplasmic reticulum


Endoscopic ultrasound-guided fine needle aspiration


Genetically engineered mouse models


Intraductal papillary mucinous neoplasm


Janus-activated kinase




Pancreatic intraepithelial neoplasia


Pancreatic ductal adenocarcinoma


Pancreatic duct ligation


Pancreatic stellate cells


Transforming growth factor beta


Tumor necrosis factor alpha


Wild type


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Cancer Progression and Metastasis Group, Institute for Cancer ResearchMedical University WienViennaAustria
  2. 2.Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre, CNIOMadridSpain
  3. 3.Departament de Ciències Experimentals i de la SalutUniversitat Pompeu FabraBarcelonaSpain
  4. 4.CIBERONCMadridSpain

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