Metabolic Targeting as an Anticancer Strategy: Dawn of a New Era?

  title={Metabolic Targeting as an Anticancer Strategy: Dawn of a New Era?},
  author={James G. Pan and Tak Wah Mak},
  journal={Science's STKE},
  pages={pe14 - pe14}
As a result of a spectrum of mitochondrial defects, tumor cells often preferentially use glycolysis to generate adenosine triphosphate (ATP), even in the presence of oxygen, a phenomenon known as aerobic glycolysis, or the "Warburg effect." Dichloroacetate (DCA) is an inhibitor of mitochondrial pyruvate dehydrogenase kinase (PDK), which inhibits pyruvate dehydrogenase (PDH), a gatekeeping enzyme for the entry of pyruvate into the mitochondrial tricarboxylic acid (TCA) cycle. In mice, DCA… 

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Anticancer drugs that target metabolism: Is dichloroacetate the new paradigm?

The fact that DCA has better in vivo activity than in vitro activity suggests that there are unique aspects of solid tumor growth and metabolism that are difficult to recapitulate in vitro and may be important in determining the effectiveness of this class of drugs.

Review of aerobic glycolysis and its key enzymes – new targets for lung cancer therapy

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The Warburg effect: molecular aspects and therapeutic possibilities

There is certainly a strong link between the genetic factors, epigenetic modulation, cancer immunosurveillance and the Warburg effect, which will be discussed in this review.

The heme precursor 5-aminolevulinic acid disrupts the Warburg effect in tumor cells and induces caspase-dependent apoptosis.

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3-bromopyruvate: Targets and outcomes

  • M. Shoshan
  • Biology, Chemistry
    Journal of Bioenergetics and Biomembranes
  • 2012
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Metabolic Modulation of Glioblastoma with Dichloroacetate

Dichloroacetate appears to be safe to give to humans at doses that are required for pyruvate dehydrogenase inhibition, and can be added to a growing group of metabolic modulators that may prove useful in cancer therapy.

Neue molekulare Signalwege und ihr therapeutisches Potential in der Krebsbehandlung

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Glycolysis inhibition for anticancer treatment

The increased dependence of cancer cells on glycolytic pathway for ATP generation provides a biochemical basis for the design of therapeutic strategies to preferentially kill cancer cells by pharmacological inhibition of Glycolysis.

p53 Regulates Mitochondrial Respiration

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Fatty acid oxidation is a dominant bioenergetic pathway in prostate cancer

  • Y. Liu
  • Biology, Chemistry
    Prostate Cancer and Prostatic Diseases
  • 2006
Dominant fatty acid metabolism rather than glycolysis has the potential to be the basis for imaging diagnosis and targeted treatment of prostate cancer.

Orlistat Is a Novel Inhibitor of Fatty Acid Synthase with Antitumor Activity

Surprisingly, a new molecular target and a potential new application for Orlistat are found, a novel inhibitor of the thioesterase domain of fatty acid synthase, an enzyme strongly linked to tumor progression.

Why do cancers have high aerobic glycolysis?

It is proposed that persistent metabolism of glucose to lactate even in aerobic conditions is an adaptation to intermittent hypoxia in pre-malignant lesions, which leads to microenvironmental acidosis requiring evolution to phenotypes resistant to acid-induced cell toxicity.

The glucose dependence of Akt-transformed cells can be reversed by pharmacologic activation of fatty acid β-oxidation

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