Harnessing metabolic dependencies in pancreatic cancers

Nat Rev Gastroenterol Hepatol. 2021 Jul;18(7):482-492. doi: 10.1038/s41575-021-00431-7. Epub 2021 Mar 19.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with a 5-year survival rate of <10%. The tumour microenvironment (TME) of PDAC is characterized by excessive fibrosis and deposition of extracellular matrix, termed desmoplasia. This unique TME leads to high interstitial pressure, vascular collapse and low nutrient and oxygen diffusion. Together, these factors contribute to the unique biology and therapeutic resistance of this deadly tumour. To thrive in this hostile environment, PDAC cells adapt by using non-canonical metabolic pathways and rely on metabolic scavenging pathways such as autophagy and macropinocytosis. Here, we review the metabolic pathways that PDAC use to support their growth in the setting of an austere TME. Understanding how PDAC tumours rewire their metabolism and use scavenging pathways under environmental stressors might enable the identification of novel therapeutic approaches.

Publication types

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

MeSH terms

  • Carcinoma, Pancreatic Ductal / metabolism
  • Humans
  • Metabolic Networks and Pathways
  • Pancreatic Neoplasms / metabolism*
  • Tumor Microenvironment / physiology*