The Mitochondrion as an Emerging Therapeutic Target in Cancer

Trends Mol Med. 2020 Jan;26(1):119-134. doi: 10.1016/j.molmed.2019.06.009. Epub 2019 Jul 18.

Abstract

Mitochondria have emerged as important pharmacological targets because of their key role in cellular proliferation and death. In tumor tissues, mitochondria can switch metabolic phenotypes to meet the challenges of high energy demand and macromolecular synthesis. Furthermore, mitochondria can engage in crosstalk with the tumor microenvironment, and signals from cancer-associated fibroblasts can impinge on mitochondria. Cancer cells can also acquire a hybrid phenotype in which both glycolysis and oxidative phosphorylation (OXPHOS) can be utilized. This hybrid phenotype can facilitate metabolic plasticity of cancer cells more specifically in metastasis and therapy-resistance. In light of the metabolic heterogeneity and plasticity of cancer cells that had until recently remained unappreciated, strategies targeting cancer metabolic dependency appear to be promising in the development of novel and effective cancer therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Energy Metabolism / physiology*
  • Glycolysis / physiology
  • Humans
  • Mitochondria / physiology*
  • Neoplasms / physiopathology*
  • Oxidative Phosphorylation
  • Tumor Microenvironment / physiology