ArticleInternational journal of molecular sciences2020
Dichloroacetate Radiosensitizes Hypoxic Breast Cancer Cells.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Current hotspots and trends in cancer metabolic reprogramming: a scientometric analysis.Frontiers in immunology · 2024Pooled it
- Mitochondria-targeted strategies in cancer radiotherapy: from ROS regulation to immunogenic cell death.Frontiers in cell and developmental biology · 2026Review
- Inhibition of PDK modulates radiotherapy resistance in gastric cancer.Discover oncology · 2025Article
- Dichloroacetate and Salinomycin as Therapeutic Agents in Cancer.Medical sciences (Basel, Switzerland) · 2025Review
- Metformin and glioma: Targeting metabolic dysregulation for enhanced therapeutic outcomes.Translational oncology · 2025Review
- Lactate-mediated metabolic reprogramming of tumor-associated macrophages: implications for tumor progression and therapeutic potential.Frontiers in immunology · 2025Review
- Targeting Metabolic-Redox Nexus to Regulate Drug Resistance: From Mechanism to Tumor Therapy.Antioxidants (Basel, Switzerland) · 2024Review
- Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Regulating mitochondrial metabolism by targeting pyruvate dehydrogenase with dichloroacetate, a metabolic messenger.Biochimica et biophysica acta. Molecular basis of disease · 2023Review
- Metabolic heterogeneity in early-stage lung adenocarcinoma revealed by RNA-seq and scRNA-seq.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Article
- Novel insight into metabolic reprogrammming in cancer radioresistance: A promising therapeutic target in radiotherapy.International journal of biological sciences · 2023Review
- Inhibition of Phosphoglycerate Dehydrogenase Radiosensitizes Human Colorectal Cancer Cells under Hypoxic Conditions.Cancers · 2022Article
- Design, Synthesis, and Molecular Docking Studies of Curcumin Hybrid Conjugates as Potential Therapeutics for Breast Cancer.Pharmaceuticals (Basel, Switzerland) · 2022Article
- 3D Breast Tumor Models for Radiobiology Applications.Cancers · 2021Review
- Review
- Chimeric Drug Design with a Noncharged Carrier for Mitochondrial Delivery.Pharmaceutics · 2021Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Mitochondrial metabolism is an attractive target for cancer therapy. Reprogramming metabolic pathways can potentially sensitize tumors with limited treatment options, such as triple-negative breast cancer (TNBC), to chemo- and/or radiotherapy. Dichloroacetate (DCA) is a specific inhibitor of the pyruvate dehydrogenase kinase (PDK), which leads to enhanced reactive oxygen species (ROS) production. ROS are the primary effector molecules of radiation and an increase hereof will enhance the radioresponse. In this study, we evaluated the effects of DCA and radiotherapy on two TNBC cell lines, namely EMT6 and 4T1, under aerobic and hypoxic conditions. As expected, DCA treatment decreased phosphorylated pyruvate dehydrogenase (PDH) and lowered both extracellular acidification rate (ECAR) and lactate production. Remarkably, DCA treatment led to a significant increase in ROS production (up to 15-fold) in hypoxic cancer cells but not in aerobic cells. Consistently, DCA radiosensitized hypoxic tumor cells and 3D spheroids while leaving the intrinsic radiosensitivity of the tumor cells unchanged. Our results suggest that although described as an oxidative phosphorylation (OXPHOS)-promoting drug, DCA can also increase hypoxic radioresponses. This study therefore paves the way for the targeting of mitochondrial metabolism of hypoxic cancer cells, in particular to combat radioresistance.
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Registered trials
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.