Pancreatic intraepithelial neoplasia and pancreatic tumorigenesis: Of mice and men

Niki A. Ottenhof, Anya N A Milne, Folkert H M Morsink, Paul Drillenburg, Fiebo J W Ten Kate, Anirban Maitra, G. Johan Offerhaus

Research output: Contribution to journalArticlepeer-review

Abstract

Context.-Pancreatic cancer has a poor prognosis with a 5-year survival of less than 5%. Early detection is at present the only way to improve this outlook. This review focuses on the recent advances in our understanding of pancreatic carcinogenesis, the scientific evidence for a multi-staged tumor progression, and the role genetically engineered mouse models can play in recapitulating the natural course and biology of human disease. Objectives.-To illustrate the stepwise tumor progression of pancreatic cancer and genetic alterations within the different stages of progression and to review the findings made with genetically engineered mouse models concerning pancreatic carcinogenesis. Data Sources.-A review of recent literature on pancreatic tumorigenesis and genetically engineered mouse models. Conclusions.-Pancreatic cancer develops through stepwise tumor progression in which preinvasive stages, called pancreatic intraepithelial neoplasia, precede invasive pancreatic cancer. Genetic alterations in oncogenes and tumor suppressor genes underlying pancreatic cancer are also found in pancreatic intraepithelial neoplasia. These mutations accumulate during progression through the consecutive stages of pancreatic intraepithelial neoplasia lesions. Also in genetically engineered mouse models of pancreatic ductal adenocarcinoma, tumorigenesis occurs through stepwise progression via consecutive mouse pancreatic intraepithelial neoplasia, and these models provide important tools for clinical applications. Nevertheless differences between mice and men still remain.

Original languageEnglish (US)
Pages (from-to)375-381
Number of pages7
JournalArchives of Pathology and Laboratory Medicine
Volume133
Issue number3
StatePublished - Mar 2009

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology

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