Mouse models of pancreatic cancer

World J Gastroenterol. 2012 Mar 28;18(12):1286-94. doi: 10.3748/wjg.v18.i12.1286.


Pancreatic cancer is one of the most lethal of human malignancies ranking 4th among cancer-related death in the western world and in the United States, and potent therapeutic options are lacking. Although during the last few years there have been important advances in the understanding of the molecular events responsible for the development of pancreatic cancer, currently specific mechanisms of treatment resistance remain poorly understood and new effective systemic drugs need to be developed and probed. In vivo models to study pancreatic cancer and approach this issue remain limited and present different molecular features that must be considered in the studies depending on the purpose to fit special research themes. In the last few years, several genetically engineered mouse models of pancreatic exocrine neoplasia have been developed. These models mimic the disease as they reproduce genetic alterations implicated in the progression of pancreatic cancer. Genetic alterations such as activating mutations in KRas, or TGFb and/or inactivation of tumoral suppressors such as p53, INK4A/ARF BRCA2 and Smad4 are the most common drivers to pancreatic carcinogenesis and have been used to create transgenic mice. These mouse models have a spectrum of pathologic changes, from pancreatic intraepithelial neoplasia to lesions that progress histologically culminating in fully invasive and metastatic disease and represent the most useful preclinical model system. These models can characterize the cellular and molecular pathology of pancreatic neoplasia and cancer and constitute the best tool to investigate new therapeutic approaches, chemopreventive and/or anticancer treatments. Here, we review and update the current mouse models that reproduce different stages of human pancreatic ductal adenocarcinoma and will have clinical relevance in future pancreatic cancer developments.

Keywords: K-Ras; Mouse models; Pancreatic cancer; Transgenic; Xenografts.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • BRCA2 Protein / genetics
  • BRCA2 Protein / metabolism
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Disease Models, Animal*
  • Disease Progression
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Mice
  • Mice, Transgenic
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / physiopathology*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins p21(ras)
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transplantation, Heterologous
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • ras Proteins / genetics
  • ras Proteins / metabolism


  • BHLHA15 protein, human
  • BRCA2 Protein
  • Basic Helix-Loop-Helix Transcription Factors
  • Cyclin-Dependent Kinase Inhibitor p16
  • Homeodomain Proteins
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Trans-Activators
  • Tumor Suppressor Protein p53
  • pancreatic and duodenal homeobox 1 protein
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins