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Special Issue "Dichloroacetate (DCA) and Cancer: Advancing DCA to a Cancer Therapeutic"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 31 December 2021.

Special Issue Editor

Dr. Anneke Blackburn
E-Mail Website
Guest Editor
Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia

Special Issue Information

Dear Colleagues,

The recognition of altered metabolism as a hallmark of cancer has led to much interest in the potential of targeting the metabolic phenotype of cancer cells as a therapeutic approach. An important component of the phenotype is the glycolytic phenotype, or Warburg effect, which can contribute to many other phenotypes of cancer, such as drug resistance and stemness. At this stage, however, agents specifically targeting the glycolytic phenotype are still limited to clinical trials.

Dichloroacetate, which is an inhibitor of pyruvate dehydrogenase kinases, is a good candidate for cancer therapy. With decades of clinical use in congenital lactic acidosis, its use in a small number of early phase clinical trials for cancer therapy has been published. The next steps for clinical trials involve identifying those cancer types most appropriate for DCA treatment, deciding which combination therapies to test, and developing a better understanding of the effects of altering metabolism on cancer cell phenotypes, such as metastatic behavior and drug resistance. This requires a deeper molecular understanding of the actions of DCA, and identification of biomarkers that may predict which cancers will respond.

In this Special Issue of IJMS, we are seeking papers (original, reviews, communications, and new concepts) that can contribute to the molecular and pre-clinical knowledge base around the actions of DCA on cancer cells and cancer microenvironments, to inform the future clinical trials of DCA. Topics of interest include, but are not limited to the following:

  • Metabolic and gene expression signatures and readouts of anti-cancer activities of DCA
  • Additional mechanisms and pathways of action of DCA with implications for cancer therapy
  • Investigations in pre-clinical models of cancer
  • Activity and molecular mechanisms of DCA in combination with other therapies
  • Novel formulations of DCA
  • Investigations of the role and regulation of pyruvate and lactate metabolism in cancer
  • Investigations of other pyruvate dehydrogenase kinase inhibitors

Dr. Anneke Blackburn
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Pyruvate dehydrogenase
  • Pyruvate dehydrogenase kinase inhibitor
  • PDK2
  • Dichloroacetate
  • Cancer glycolytic phenotype
  • Warburg effect
  • Mitochondrial activation
  • Biomarker

Published Papers (1 paper)

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Review

Review
Targeting Glucose Metabolism of Cancer Cells with Dichloroacetate to Radiosensitize High-Grade Gliomas
Int. J. Mol. Sci. 2021, 22(14), 7265; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147265 - 06 Jul 2021
Viewed by 954
Abstract
As the cornerstone of high-grade glioma (HGG) treatment, radiotherapy temporarily controls tumor cells via inducing oxidative stress and subsequent DNA breaks. However, almost all HGGs recur within months. Therefore, it is important to understand the underlying mechanisms of radioresistance, so that novel strategies [...] Read more.
As the cornerstone of high-grade glioma (HGG) treatment, radiotherapy temporarily controls tumor cells via inducing oxidative stress and subsequent DNA breaks. However, almost all HGGs recur within months. Therefore, it is important to understand the underlying mechanisms of radioresistance, so that novel strategies can be developed to improve the effectiveness of radiotherapy. While currently poorly understood, radioresistance appears to be predominantly driven by altered metabolism and hypoxia. Glucose is a central macronutrient, and its metabolism is rewired in HGG cells, increasing glycolytic flux to produce energy and essential metabolic intermediates, known as the Warburg effect. This altered metabolism in HGG cells not only supports cell proliferation and invasiveness, but it also contributes significantly to radioresistance. Several metabolic drugs have been used as a novel approach to improve the radiosensitivity of HGGs, including dichloroacetate (DCA), a small molecule used to treat children with congenital mitochondrial disorders. DCA reverses the Warburg effect by inhibiting pyruvate dehydrogenase kinases, which subsequently activates mitochondrial oxidative phosphorylation at the expense of glycolysis. This effect is thought to block the growth advantage of HGGs and improve the radiosensitivity of HGG cells. This review highlights the main features of altered glucose metabolism in HGG cells as a contributor to radioresistance and describes the mechanism of action of DCA. Furthermore, we will summarize recent advances in DCA’s pre-clinical and clinical studies as a radiosensitizer and address how these scientific findings can be translated into clinical practice to improve the management of HGG patients. Full article
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