Non-Hodgkin's Lymphoma Reversal with Dichloroacetate

Flavin, Dana

doi:10.1155/2010/414726

Cited by 15 publications

(14 citation statements)

References 22 publications

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“…DCA has been used in medicine for over 30 years to treat metabolic disorders, including lactic acidosis [ 7 , 8 ]. Furthermore, DCA has shown clinical efficacy for the treatment of glioblastoma [ 9 ] and complete remission of a patient with non-Hodgkin's lymphoma was reported after self-administration of DCA [ 10 ]. However, the mechanisms responsible for DCA-induced tumor regression have not been clearly elucidated and the effect of DCA in different tumors is still controversial [ 10 – 16 ].…”

Section: Introductionmentioning

confidence: 99%

The presence of wild type p53 in hematological cancers improves the efficacy of combinational therapy targeting metabolism

et al. 2015

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Manipulation of metabolic pathways in hematological cancers has therapeutic potential. Here, we determined the molecular mechanism of action of the metabolic modulator dichloroacetate (DCA) in leukemic cells. We found that DCA induces the AMP-activated protein kinase (AMPK)/p53 pathway with increased efficacy in tumors expressing wild type (wt p53). Clinically relevant, low concentrations of doxorubicin synergize in vitro and in vivo with DCA to further enhance p53 activation and to block tumor progression. Leukemia cell lines and primary leukemic cells containing mutant p53 are resistant to the above-described combination approach. However, DCA synergized with the Hsp90 inhibitor 17-AAG to specifically eliminate these cells. Our studies strongly indicate that depending on the p53 status, different combination therapies would provide better treatment with decreased side effects in hematological cancers.

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Section: Introductionmentioning

confidence: 99%

The presence of wild type p53 in hematological cancers improves the efficacy of combinational therapy targeting metabolism

et al. 2015

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“…Moreover a case of a patient with Non-Hodgkin's Lymphoma who showed a complete remission after administering DCA was reported [18].…”

Section: Introductionmentioning

confidence: 99%

Influence of Dichloroacetate (DCA) on Lactate Production and Oxygen Consumption in Neuroblastoma Cells: Is DCA a Suitable Drug for Neuroblastoma Therapy?

Niewisch¹,

Kuçi²,

Wolburg

et al. 2012

Cell Physiol Biochem

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Many cancer cells metabolize glucose preferentially via pyruvate to lactate instead to CO₂ and H₂O (oxidative phosphorylation) even in the presence of oxygen (Warburg effect). Dichloroacetate (DCA) is a drug which is able to shift pyruvate metabolism from lactate to acetyl-CoA (tricarboxylic acid cycle) by indirect activation of pyruvate dehydrogenase (PDH). This can subsequently lead to an increased flow of oxygen in the respiratory chain, associated with enhanced generation of reactive oxygen species (ROS) which may cause apoptosis. In order to investigate if DCA may be suitable for neuroblastoma therapy, it was investigated on three human neuroblastoma cell lines whether DCA can reduce lactate production and enhance oxygen consumption. The data show, that DCA (in the low millimolar range) is able to reduce lactate production, but there was only a slight shift to increased oxygen consumption and almost no effect on cell vitality, proliferation and apoptosis of the three cell lines investigated. Therefore, DCA at low millimolar concentrations seems to be only of minor efficacy for neuroblastoma treatment.

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“…After four months of DCA intake, PET/CT showed complete remission of NHL. However, this single observation was not associated with any follow-up period (10).…”

Section: Discussionmentioning

confidence: 60%

Dichloroacetate-Induced Neuropathy in High Grade Follicular Lymphoma Patient

Djordjević¹,

Petković²

2019

AMM

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Curative therapy for follicular lymphomas (FLs) has not been established yet. FLs respond well to chemotherapy and radiation. A large number of current studies confirmed an improved overall response if rituximab was added to chemotherapy. Dichloroacetate (DCA) can be used to inhibit tumor growth. There have been reports that DCA leads to neuropathy. In non-Hodgkin's lymphoma (NHL), DCA leads to antineoplastic action against cell lines and apoptosis of tumor cells, which reduces the metabolism and the number of tumor cells. We present a patient with NHL-FL Grade 3a who took alternatively DCA therapy. In our case report, DCA did not show any treatment benefit but only serious sensorimotor neuropathy as a result of DCA therapy.

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Non-Hodgkin's Lymphoma Reversal with Dichloroacetate

Cited by 15 publications

References 22 publications

The presence of wild type p53 in hematological cancers improves the efficacy of combinational therapy targeting metabolism

The presence of wild type p53 in hematological cancers improves the efficacy of combinational therapy targeting metabolism

Influence of Dichloroacetate (DCA) on Lactate Production and Oxygen Consumption in Neuroblastoma Cells: Is DCA a Suitable Drug for Neuroblastoma Therapy?

Dichloroacetate-Induced Neuropathy in High Grade Follicular Lymphoma Patient

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