KRAS: feeding pancreatic cancer proliferation

Trends Biochem Sci. 2014 Feb;39(2):91-100. doi: 10.1016/j.tibs.2013.12.004. Epub 2014 Jan 2.


Oncogenic KRAS mutation is the signature genetic event in the progression and growth of pancreatic ductal adenocarcinoma (PDAC), an almost universally fatal disease. Although it has been appreciated for some time that nearly 95% of PDAC harbor mutationally activated KRAS, to date no effective treatments that target this mutant protein have reached the clinic. A number of studies have shown that oncogenic KRAS plays a central role in controlling tumor metabolism by orchestrating multiple metabolic changes including stimulation of glucose uptake, differential channeling of glucose intermediates, reprogrammed glutamine metabolism, increased autophagy, and macropinocytosis. We review these recent findings and address how they may be applied to develop new PDAC treatments.

Keywords: autophagy; glutaminolysis; glycolysis; macropinocytosis; metabolism.

Publication types

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

MeSH terms

  • Autophagy
  • Carcinoma, Pancreatic Ductal / enzymology*
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Glucose / metabolism*
  • Glutamine / metabolism*
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Mutation
  • Pancreatic Neoplasms / enzymology*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • Pinocytosis
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins p21(ras)
  • Signal Transduction
  • ras Proteins / genetics
  • ras Proteins / metabolism*


  • Isoenzymes
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Glutamine
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins
  • Glucose