ArticleCell reports2020
Dynamic Imaging of LDH Inhibition in Tumors Reveals Rapid In Vivo Metabolic Rewiring and Vulnerability to Combination Therapy.
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Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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72citing papers in PubMed
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72 citing papers in PubMed, 116 citations in OpenAlex.
- LDH isozymes as targets for cancer therapy.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Lactate as a Signaling Molecule in the Tumor Microenvironment: Implications for Cancer Progression.Biochemical genetics · 2026Review
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Clinical implications of lactylation modification in digestive system tumors (Review).Oncology letters · 2026Review
- Lactate and lactylation: mechanisms, function, diseases, and therapeutic targets.Molecular biomedicine · 2026Review
- Lactate-lactylation in tumor angiogenesis and progression: mechanisms, biomarker potential, and therapeutic implications.Biomarker research · 2026Review
- Lactylation in cancer: molecular mechanisms and advances in clinical study.Molecular cancer · 2026Review
- Lactate: elucidating its indispensable role in human health.Molecular cancer · 2026Review
- Metabolic rewiring of the tumor microenvironment: therapeutic intervention of multi-pathway adaptations to impede cancer metastasis.Frontiers in molecular biosciences · 2026Review
- BFAR Promotes Neutrophil Infiltration and Immunosuppressive Reprogramming through the PRP19-YBX1 Axis to Induce Immune Evasion in Gastric Cancer.Cancer immunology research · 2025Article
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- Breaking the vicious cycle: Multifunctional nanomaterials targeting Tumor metabolic reprogramming to overcome T cell exhaustion and bone repair failure in bone tumors.Materials today. Bio · 2025Review
- Lactylation-mediated miRNA regulation in cancer therapy resistance.Journal of translational medicine · 2025Review
- Review
- Glucose metabolism and its direct action in cancer and immune regulation: opportunities and challenges for metabolic targeting.Journal of biomedical science · 2025Review
- Lactate metabolism and lactylation in breast cancer: mechanisms and implications.Cancer metastasis reviews · 2025Review
- Assessment of early response to neoadjuvant chemotherapy in multi-site high-grade serous ovarian cancer using hyperpolarized-EJNMMI research · 2025Article
- Lactate and lactylation in cancer.Signal transduction and targeted therapy · 2025Review
- Targeting NAD+ Metabolism Vulnerability in FH-Deficient Hereditary Leiomyomatosis and Renal Cell Carcinoma with the Novel NAMPT Inhibitor OT-82.Molecular cancer therapeutics · 2025Article
- Enhancing Radiation Therapy Response in Prostate Cancer Through Metabolic Modulation by Mito-Lonidamine: AInternational journal of molecular sciences · 2025Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
41 authors at 11 institutions in 2 countries.
Nobu OshimaUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Ryo IshidaUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Shun KishimotoRadiation Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Kristin BeebeUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Jeffrey R BrenderRadiation Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Kazutoshi YamamotoRadiation Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Daniel UrbanChemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Ganesha RaiChemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Michelle S JohnsonMitochondrial Medicine Laboratory, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Gloria BenavidesMitochondrial Medicine Laboratory, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Giuseppe L SquadritoMitochondrial Medicine Laboratory, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Dan CrooksUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Joseph JacksonUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Abhinav JoshiDepartment of Cell Biology, University of Geneva, 1211 Geneva 4, Switzerland.
Bryan T MottChemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Jonathan H ShrimpChemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Michael A MosesUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Min-Jung LeeDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Akira YunoDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Tobie D LeeChemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Xin HuChemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Tamara AndersonUniversity of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Donna KusewittUniversity of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Helen H HathawayUniversity of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Ajit JadhavChemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Didier PicardDepartment of Cell Biology, University of Geneva, 1211 Geneva 4, Switzerland.
Jane B TrepelDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
James B MitchellRadiation Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Gordon M StottLeidos Biomedical, Frederick National Laboratory for Cancer Research, Frederick, MD 24060, USA.
William MooreLeidos Biomedical, Frederick National Laboratory for Cancer Research, Frederick, MD 24060, USA.
Anton SimeonovChemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Larry A SklarUniversity of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Jeffrey P NorenbergUniversity of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
W Marston LinehanUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
David J MaloneyChemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Chi V DangLudwig Institute for Cancer Research, New York, NY 10017, USA; The Wistar Institute, Philadelphia, PA 19104, USA.
Alex G WatersonDepartment of Chemistry, Vanderbilt University, Nashville, TN 37240, USA.
Matthew HallChemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Victor M Darley-UsmarMitochondrial Medicine Laboratory, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Murali C KrishnaRadiation Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Leonard M NeckersUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address: neckersl@mail.nih.gov.
Center for Cancer Research · USNational Cancer Institute · USNational Center for Advancing Translational Sciences · USNational Institutes of Health · USUniversity of New Mexico · USLeidos (United States) · USMitochondria Research and Medicine Society · USUniversity of Alabama at Birmingham · USUniversity of Geneva · CHThe Wistar Institute · USVanderbilt University · US
Funding
Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Maureen E. Murphy · 1985 to 2026
$75.9MMolecular Therapeutics of Kidney Cancer: VHL Gene and Fumarate Hydratase GeneZIABC011038 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI LINEHAN, WILLIAM MARSTON · 2009 to 2025
$29.8MClinical Nursing and Data Management CoreZIDBC011089 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI LINEHAN, WILLIAM MARSTON · 2009 to 2025
$17.4MModulation of Therapeutic ResponseZIASC006321 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI MITCHELL, JAMES · 2009 to 2025
$17.3MSignal Transduction Events and the Regulation of Cell GrowthZICSC006743 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI TREPEL, JANE B · 2009 to 2023
$13.8MRole of fumarate hydratase loss in development of HLRCC hereditary kidney cancerZIABC010683 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI NECKERS, LEONARD · 2009 to 2024
$8.6MMYC--TRANSCRIPTION AND INTERACTION WITH P107R01CA051497 · NCI · WISTAR INSTITUTE · PI DANG, CHI V. · 1995 to 2025
$5.3MIntramural NIH HHS ZIA BC010683NCI NIH HHS P30 CA010815NCI NIH HHS R01 CA051497
Abstract
The reliance of many cancers on aerobic glycolysis has stimulated efforts to develop lactate dehydrogenase (LDH) inhibitors. However, despite significant efforts, LDH inhibitors (LDHi) with sufficient specificity and in vivo activity to determine whether LDH is a feasible drug target are lacking. We describe an LDHi with potent, on-target, in vivo activity. Using hyperpolarized magnetic resonance spectroscopic imaging (HP-MRSI), we demonstrate in vivo LDH inhibition in two glycolytic cancer models, MIA PaCa-2 and HT29, and we correlate depth and duration of LDH inhibition with direct anti-tumor activity. HP-MRSI also reveals a metabolic rewiring that occurs in vivo within 30 min of LDH inhibition, wherein pyruvate in a tumor is redirected toward mitochondrial metabolism. Using HP-MRSI, we show that inhibition of mitochondrial complex 1 rapidly redirects tumor pyruvate toward lactate. Inhibition of both mitochondrial complex 1 and LDH suppresses metabolic plasticity, causing metabolic quiescence in vitro and tumor growth inhibition in vivo.
Indexed as
AnimalsDrug Therapy, CombinationHumansL-Lactate DehydrogenaseMiceNeoplasmsL-Lactate Dehydrogenasecancerhyperpolarized magnetic resonance spectroscopic imaginglactate dehydrogenasemetabolic fluxmetabolic imagingpyruvate metabolism
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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.