Is reliance on mitochondrial respiration a "chink in the armor" of therapy-resistant cancer?

Cancer Cell. 2014 Dec 8;26(6):788-795. doi: 10.1016/j.ccell.2014.10.001.

Abstract

A series of recent reports has suggested PGC1α-driven upregulation of mitochondrial oxidative phosphorylation as a selective vulnerability of drug-resistant cancers. Accordingly, chemical inhibitors of respiration led to selective eradication of such cancer cells due to their preferential sensitivity to mitochondrial production of reactive oxygen species. These insights create a timely opportunity for a biomarker guided application of already existing and newly emerging mitochondrial inhibitors in recurrent drug-resistant cancer, including lymphomas, melanomas, and other malignant diseases marked by increased mitochondrial respiration.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Drug Resistance, Neoplasm / drug effects*
  • Humans
  • Mitochondria / metabolism*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Oxidative Phosphorylation / drug effects
  • Oxidative Stress / drug effects
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Reactive Oxygen Species / metabolism
  • Transcription Factors / metabolism*

Substances

  • Antineoplastic Agents
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Reactive Oxygen Species
  • Transcription Factors