Oxidative phosphorylation as a potential therapeutic target for cancer therapy

Int J Cancer. 2020 Jan 1;146(1):10-17. doi: 10.1002/ijc.32616. Epub 2019 Sep 11.


In contrast to prior belief, cancer cells require oxidative phosphorylation (OXPHOS) to strive, and exacerbated OXPHOS dependency frequently characterizes cancer stem cells, as well as primary or acquired resistance against chemotherapy or tyrosine kinase inhibitors. A growing arsenal of therapeutic agents is being designed to suppress the transfer of mitochondria from stromal to malignant cells, to interfere with mitochondrial biogenesis, to directly inhibit respiratory chain complexes, or to disrupt mitochondrial function in other ways. For the experimental treatment of cancers, OXPHOS inhibitors can be advantageously combined with tyrosine kinase inhibitors, as well as with other strategies to inhibit glycolysis, thereby causing a lethal energy crisis. Unfortunately, most of the preclinical data arguing in favor of OXPHOS inhibition have been obtained in xenograft models, in which human cancer cells are implanted in immunodeficient mice. Future studies on OXPHOS inhibitors should elaborate optimal treatment schedules and combination regimens that stimulate-or at least are compatible with-anticancer immune responses for long-term tumor control.

Keywords: Warburg phenomenon; bioenergetics; immunotherapy; metabolism; mitochondrial respiration.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Carcinogenesis
  • Glycolysis
  • Humans
  • Mice
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / metabolism
  • Organelle Biogenesis
  • Oxidative Phosphorylation*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Protein-Tyrosine Kinases