Pancreatic cancer biology and genetics from an evolutionary perspective

Nat Rev Cancer. 2016 Sep;16(9):553-65. doi: 10.1038/nrc.2016.66. Epub 2016 Jul 22.


Cancer is an evolutionary disease, containing the hallmarks of an asexually reproducing unicellular organism subject to evolutionary paradigms. Pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer) is a particularly robust example of this phenomenon. Genomic features indicate that pancreatic cancer cells are selected for fitness advantages when encountering the geographic and resource-depleted constraints of the microenvironment. Phenotypic adaptations to these pressures help disseminated cells to survive in secondary sites, a major clinical problem for patients with this disease. In this Review we gather the wide-ranging aspects of pancreatic cancer research into a single concept rooted in Darwinian evolution, with the goal of identifying novel insights and opportunities for study.

Publication types

  • Review

MeSH terms

  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / immunology
  • Carcinoma, Pancreatic Ductal / pathology*
  • Cell Division
  • Cell Survival
  • Cell Transformation, Neoplastic / genetics
  • Clone Cells
  • Evolution, Molecular
  • Genes, p16
  • Genes, p53
  • Genes, ras
  • Genetic Heterogeneity
  • Humans
  • Mutation
  • Neoplasm Metastasis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology
  • Neoplastic Stem Cells
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / pathology*
  • Risk Factors
  • Selection, Genetic*
  • Smad4 Protein / genetics
  • Stromal Cells / physiology
  • Tumor Microenvironment


  • Neoplasm Proteins
  • SMAD4 protein, human
  • Smad4 Protein