title: Out of Warburg effect: An effective cancer treatment targeting the tumor specific metabolism and dysregulated pH.
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.
authors.affiliation: Assistance Publique des Hôpitaux de Paris, France. Electronic address: dr.Laurentschwartz@gmail.com.
authors.forename: Laurent
authors.initials: L
authors.lastname: Schwartz
authors.affiliation: Biology Department, Boston College, Chestnut Hill, MA, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Seyfried
authors.affiliation: Al-Gahd International College for Applied Medical Sciences, Al-Madinah Al-Munawarah, Saudi Arabia; Center for Evolution and Cancer, University of California San Francisco, USA.
authors.forename: Khalid O
authors.initials: KO
authors.lastname: Alfarouk
authors.affiliation: Laboratoire d'informatique Ecole Polytechnique, Palaiseau, France.
authors.forename: Jorgelindo
authors.initials: J
authors.lastname: Da Veiga Moreira
authors.affiliation: Department of Therapeutic Research and Medicine Evaluation, National Institute of Health, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fais
mesh_terms: D000818:Animals; D002951:Citrates / Q000008:administration & dosage; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism*; D008063:Thioctic Acid / Q000008:administration & dosage
chemical_list: D002951:Citrates; D008063:Thioctic Acid; C007999:hydroxycitric acid; D010100:Oxygen
keywords: ATP; Intracellular alkalosis; Ketogenic diet; Metabolic treatment; Unification theory; Warburg’s effect