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Matti Narkia

Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer - British J... - 1 views

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    Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer.
    Michelakis ED, Webster L, Mackey JR.
    Br J Cancer. 2008 Oct 7;99(7):989-94. Epub 2008 Sep 2. Review.
    PMID: 18766181
    doi:10.1038/sj.bjc.6604554

    The unique metabolism of most solid tumours (aerobic glycolysis, i.e., Warburg effect) is not only the basis of diagnosing cancer with metabolic imaging but might also be associated with the resistance to apoptosis that characterises cancer. The glycolytic phenotype in cancer appears to be the common denominator of diverse molecular abnormalities in cancer and may be associated with a (potentially reversible) suppression of mitochondrial function. The generic drug dichloroacetate is an orally available small molecule that, by inhibiting the pyruvate dehydrogenase kinase, increases the flux of pyruvate into the mitochondria, promoting glucose oxidation over glycolysis. This reverses the suppressed mitochondrial apoptosis in cancer and results in suppression of tumour growth in vitro and in vivo. Here, we review the scientific and clinical rationale supporting the rapid translation of this promising metabolic modulator in early-phase cancer clinical trials

    More than 40 nonrandomised trials of DCA in small cohorts of patients have been reported, but the first two randomised control trials of chronic oral therapy with DCA in congenital mitochondrial diseases were reported in 2006. In the first, a blinded placebo-controlled study was performed with oral DCA administered at 25 mg kg-1 day-1 in 30 patients with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) (Kaufmann et al, 2006). Most patients enrolled in the DCA arm developed symptomatic peripheral neuropathy, compared with 4 out of 15 in the placebo arm, leading to the termination of the study. Seventeen out of 19 patients had at least partial resolution of peripheral neurological symptoms by 9 months after discontinuation of DCA. This neurotoxicity res
Matti Narkia

A Mitochondria-K+ Channel Axis Is Suppressed in Cancer and Its Normalization Promotes A... - 0 views

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    A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth.
    Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S, Harry G, Hashimoto K, Porter CJ, Andrade MA, Thebaud B, Michelakis ED.
    Cancer Cell. 2007 Jan;11(1):37-51.
    PMID: 17222789
    doi:10.1016/j.ccr.2006.10.020
Matti Narkia

Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer - British J... - 0 views

  •  
    Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer.\nMichelakis ED, Webster L, Mackey JR.\nBr J Cancer. 2008 Oct 7;99(7):989-94. Epub 2008 Sep 2. Review.\nPMID: 18766181 \ndoi:10.1038/sj.bjc.6604554 \n
Matti Narkia

Questions over DCA 'cancer drug' - Cancer Research UK : - 1 views

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    You may have seen articles in the news about a drug called DCA (dichloroacetate), that is claimed to be cheap, safe and "kill most cancers". Understandably this has caused a great deal of interest, especially as DCA is an off-patent drug and appears to be non-toxic to humans.

    DCA has now been approved for a trial in brain cancer patients in Canada. The researchers have raised $800,000 in public donations to fund the trial
Matti Narkia

Cheap, safe drug kills most cancers - health - 17 January 2007 - New Scientist - 0 views

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    It sounds almost too good to be true: a cheap and simple drug that kills almost all cancers by switching off their "immortality". The drug, dichloroacetate (DCA), has already been used for years to treat rare metabolic disorders and so is known to be
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