More Than Meets the Eye Regarding Cancer Metabolism

Int J Mol Sci. 2021 Sep 1;22(17):9507. doi: 10.3390/ijms22179507.

Abstract

In spite of the continuous improvement in our knowledge of the nature of cancer, the causes of its formation and the development of new treatment methods, our knowledge is still incomplete. A key issue is the difference in metabolism between normal and cancer cells. The features that distinguish cancer cells from normal cells are the increased proliferation and abnormal differentiation and maturation of these cells, which are due to regulatory changes in the emerging tumour. Normal cells use oxidative phosphorylation (OXPHOS) in the mitochondrion as a major source of energy during division. During OXPHOS, there are 36 ATP molecules produced from one molecule of glucose, in contrast to glycolysis which provides an ATP supply of only two molecules. Although aerobic glucose metabolism is more efficient, metabolism based on intensive glycolysis provides intermediate metabolites necessary for the synthesis of nucleic acids, proteins and lipids, which are in constant high demand due to the intense cell division in cancer. This is the main reason why the cancer cell does not "give up" on glycolysis despite the high demand for energy in the form of ATP. One of the evolving trends in the development of anti-cancer therapies is to exploit differences in the metabolism of normal cells and cancer cells. Currently constructed therapies, based on cell metabolism, focus on the attempt to reprogram the metabolic pathways of the cell in such a manner that it becomes possible to stop unrestrained proliferation.

Keywords: Warburg effect; cancer metabolism; glutamine; glycolysis; lactate; tumour heterogeneity.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Animals
  • Glucose / metabolism*
  • Glycolysis*
  • Humans
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Oxidative Phosphorylation*

Substances

  • Adenosine Triphosphate
  • Glucose