Metabolic therapy and bioenergetic analysis: The missing piece of the puzzle

Mol Metab. 2021 Dec:54:101389. doi: 10.1016/j.molmet.2021.101389. Epub 2021 Nov 5.

Abstract

Background: Aberrant metabolism is recognized as a hallmark of cancer, a pillar necessary for cellular proliferation. Regarding bioenergetics (ATP generation), most cancers display a preference not only toward aerobic glycolysis ("Warburg effect") and glutaminolysis (mitochondrial substrate level-phosphorylation) but also toward other metabolites such as lactate, pyruvate, and fat-derived sources. These secondary metabolites can assist in proliferation but cannot fully cover ATP demands.

Scope of review: The concept of a static metabolic profile is challenged by instances of heterogeneity and flexibility to meet fuel/anaplerotic demands. Although metabolic therapies are a promising tool to improve therapeutic outcomes, either via pharmacological targets or press-pulse interventions, metabolic plasticity is rarely considered. Lack of bioenergetic analysis in vitro and patient-derived models is hindering translational potential. Here, we review the bioenergetics of cancer and propose a simple analysis of major metabolic pathways, encompassing both affordable and advanced techniques. A comprehensive compendium of Seahorse XF bioenergetic measurements is presented for the first time.

Major conclusions: Standardization of principal readouts might help researchers to collect a complete metabolic picture of cancer using the most appropriate methods depending on the sample of interest.

Keywords: Cancer; Energy metabolism; Glycolysis; Oxidative phosphorylation; Research design.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Animals
  • Cell Proliferation
  • Energy Metabolism
  • Humans
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / therapy*

Substances

  • Adenosine Triphosphate