Evidence map›Paper›PMID 34649623›Full record

ArticleCancer & metabolism2021

3-Bromopyruvate-mediated MCT1-dependent metabolic perturbation sensitizes triple negative breast cancer cells to ionizing radiation.

Irini Skaripa-Koukelli, David Hauton, John Walsby-Tickle, Eloïse Thomas, Joshua Owen, Abirami Lakshminarayanan, Sarah Able, James McCullagh, Robert C Carlisle, Katherine A Vallis

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer & metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.0field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 17 citations in OpenAlex.

  1. Natural product as a lead for impairing mitochondrial respiration in cancer cells.Journal of enzyme inhibition and medicinal chemistry · 2025
    Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Modulating Glycolysis to Improve Cancer Therapy.International journal of molecular sciences · 2023
    Review
  8. Review
  9. Review
  10. Article
  11. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Irini Skaripa-KoukelliDepartment of Engineering Science, Institute of Biomedical Engineering, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
David HautonDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, UK.
John Walsby-TickleDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, UK.
Eloïse ThomasDepartment of Oncology, Oxford Institute for Radiation Oncology, University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford, OX3 7DQ, UK.
Joshua OwenDepartment of Engineering Science, Institute of Biomedical Engineering, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
Abirami LakshminarayananDepartment of Oncology, Oxford Institute for Radiation Oncology, University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford, OX3 7DQ, UK.
Sarah AbleDepartment of Oncology, Oxford Institute for Radiation Oncology, University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford, OX3 7DQ, UK.
James McCullaghDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, UK.
Robert C CarlisleDepartment of Engineering Science, Institute of Biomedical Engineering, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
Katherine A VallisDepartment of Oncology, Oxford Institute for Radiation Oncology, University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford, OX3 7DQ, UK. katherine.vallis@oncology.ox.ac.uk.ORCID http://orcid.org/0000-0003-4672-5683
University of Oxford · GB

Funding

Biotechnology and Biological Sciences Research Council BB/R013829/1Cancer Research UK 22906Cancer Research UK 28736Cancer Research UK C5255/A15935Wellcome TrustWellcome Trust 204483/Z/16/Z
6 · The paper itself

Abstract

backgroundTriple negative breast cancer (TNBC) poses a serious clinical challenge as it is an aggressive form of the disease that lacks estrogen receptor, progesterone receptor, and ERBB2 (formerly HER2) gene amplification, which limits the treatment options. The Warburg phenotype of upregulated glycolysis in the presence of oxygen has been shown to be prevalent in TNBC. Elevated glycolysis satisfies the energy requirements of cancer cells, contributes to resistance to treatment by maintaining redox homeostasis and generating nucleotide precursors required for cell proliferation and DNA repair. Expression of the monocarboxylate transporter 1 (MCT1), which is responsible for the bidirectional transport of lactate, correlates with an aggressive phenotype and poor outcome in several cancer types, including breast cancer. In this study, 3-bromopyruvate (3BP), a lactate/pyruvate analog, was used to selectively target TNBC cells that express MCT1.

methodsThe cytotoxicity of 3BP was tested in MTT assays using human TNBC cell lines: BT20 (MCT1

resultsMetabolomic analyses showed that 3BP causes inhibition of glycolysis, disturbance of redox homeostasis, decreased nucleotide synthesis, and was accompanied by a reduction in medium acidification. In addition, 3BP potentiated the cytotoxic effect of ionizing radiation, a treatment that is frequently used in the management of TNBC.

conclusionsOverall, MCT1-mediated metabolic perturbation in combination with radiotherapy is shown to be a promising strategy for the treatment of glycolytic tumors such as TNBC, overcoming the selectivity challenges of targeting glycolysis with glucose analogs.

Indexed as

3-BromopyruvateIonizing radiationMetabolismTriple-negative breast cancer

Identifiers

PMID34649623
PMCPMC8515664
OpenAlexW3200552943

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.