Carcinogenesis of Pancreatic Ductal Adenocarcinoma

Gastroenterology. 2020 Jun;158(8):2072-2081. doi: 10.1053/j.gastro.2020.02.059. Epub 2020 Mar 19.

Abstract

Although the estimated time for development of pancreatic ductal adenocarcinoma (PDA) is more than 20 years, PDAs are usually detected at late, metastatic stages. PDAs develop from duct-like cells through a multistep carcinogenesis process, from low-grade dysplastic lesions to carcinoma in situ and eventually to metastatic disease. This process involves gradual acquisition of mutations in oncogenes and tumor suppressor genes, as well as changes in the pancreatic environment from a pro-inflammatory microenvironment that favors the development of early lesions, to a desmoplastic tumor microenvironment that is highly fibrotic and immune suppressive. This review discusses our current understanding of how PDA originates.

Keywords: Carcinogenesis; Desmoplastic Reaction; Microenvironment; Pancreatic Ductal Adenocarcinoma; Pancreatic Intraepithelial Neoplasia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Carcinoma, Pancreatic Ductal* / genetics
  • Carcinoma, Pancreatic Ductal* / metabolism
  • Carcinoma, Pancreatic Ductal* / pathology
  • Cell Lineage
  • Cell Transformation, Neoplastic* / genetics
  • Cell Transformation, Neoplastic* / metabolism
  • Cell Transformation, Neoplastic* / pathology
  • Disease Progression
  • Genetic Predisposition to Disease
  • Humans
  • Mutation
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / metabolism
  • Pancreatic Neoplasms* / pathology
  • Time Factors
  • Tumor Microenvironment*

Substances

  • Biomarkers, Tumor