Out of Warburg effect: An effective cancer treatment targeting the tumor specific metabolism and dysregulated pH

Laurent Schwartz, Thomas Seyfried, Khalid O. Alfarouk, Jorgelindo Da Veiga Moreira, Stefano Fais

Research output: Contribution to journalReview articlepeer-review

Abstract

As stated by Otto Warburg nearly a century ago, cancer is a metabolic disease, a fermentation caused by malfunctioning mitochondria, resulting in increased anabolism and decreased catabolism. Treatment should, therefore, aim at restoring the energy yield. To decrease anabolism, glucose uptake should be reduced (ketogenic diet). To increase catabolism, the oxidative phosphorylation should be restored. Treatment with a combination of α-lipoic acid and hydroxycitrate has been shown to be effective in multiple animal models. This treatment, in combination with conventional chemotherapy, has yielded extremely encouraging results in glioblastoma, brain metastasis and lung cancer. Randomized trials are necessary to confirm these preliminary data. The major limitation is the fact that the combination of α-lipoic acid and hydroxycitrate can only be effective if the mitochondria are still present and/or functional. That may not be the case in the most aggressive tumors. The increased intracellular alkalosis is a strong mitogenic signal, which bypasses most inhibitory signals. Concomitant correction of this alkalosis may be a very effective treatment in case of mitochondrial failure.

Original languageEnglish
Pages (from-to)134-138
Number of pages5
JournalSeminars in Cancer Biology
Volume43
DOIs
Publication statusPublished - Apr 1 2017

Keywords

  • ATP
  • Intracellular alkalosis
  • Ketogenic diet
  • Metabolic treatment
  • Unification theory
  • Warburg's effect

ASJC Scopus subject areas

  • Cancer Research

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