Metabolic Fitness and Plasticity in Cancer Progression

Trends Cancer. 2020 Jan;6(1):49-61. doi: 10.1016/j.trecan.2019.11.009. Epub 2020 Jan 3.

Abstract

Cancer cells have enhanced metabolic needs due to their rapid proliferation. Moreover, throughout their progression from tumor precursors to metastases, cancer cells face challenging physiological conditions, including hypoxia, low nutrient availability, and exposure to therapeutic drugs. The ability of cancer cells to tailor their metabolic activities to support their energy demand and biosynthetic needs throughout disease progression is key for their survival. Here, we review the metabolic adaptations of cancer cells, from primary tumors to therapy resistant cancers, and the mechanisms underpinning their metabolic plasticity. We also discuss the metabolic coupling that can develop between tumors and the tumor microenvironment. Finally, we consider potential metabolic interventions that could be used in combination with standard therapeutic approaches to improve clinical outcome.

Keywords: cancer; metabolic interventions; metabolism; metastasis; therapy resistance; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cell Plasticity / drug effects*
  • Citric Acid Cycle / drug effects
  • Disease Progression
  • Energy Metabolism / drug effects*
  • Epithelial-Mesenchymal Transition / drug effects
  • Humans
  • Hypoxia-Inducible Factor 1 / metabolism
  • Mice
  • Neoplasms / blood
  • Neoplasms / drug therapy
  • Neoplasms / pathology*
  • Neoplastic Cells, Circulating / drug effects
  • Neoplastic Cells, Circulating / pathology
  • Nutrients / metabolism
  • Oxidative Phosphorylation / drug effects
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • TOR Serine-Threonine Kinases / metabolism
  • Tumor Hypoxia / drug effects
  • Tumor Microenvironment / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Hypoxia-Inducible Factor 1
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases