ArticleCancer discovery2020
The Folate Cycle Enzyme MTHFR Is a Critical Regulator of Cell Response to MYC-Targeting Therapies.
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Article in Cancer discovery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18citing papers in PubMed
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18 citing papers in PubMed, 26 citations in OpenAlex.
- Splicing-associated network PAK1-CLK1/4-SRRM1 is a vulnerability to overcome chemoresistance in human and mouse acute myeloid leukemia.Science translational medicine · 2026Article
- Role of methionine metabolism in cancer: recent advances in molecular mechanisms and therapeutic implications.Experimental hematology & oncology · 2026Review
- Metabolic modulation of immune cell function: mechanisms and therapeutic implications in cancer immunotherapy.Oncogenesis · 2026Review
- Review
- Reference-guided computational framework identifies microenvironment metabolic subtypes and targets using pan-cancer single-cell datasets.Genome medicine · 2025Article
- Effects of aging and anti-aging dietary restriction on regulators of the [NADPH]/[NADPFree radical biology & medicine · 2025Review
- Interplay of YEATS2 and GCDH regulates histone crotonylation and drives EMT in head and neck cancer.eLife · 2025Article
- Advances and challenges in human 3D solid tumor models.Advanced functional materials · 2025Article
- Folate metabolism in myelofibrosis: a missing key?Annals of hematology · 2025Review
- Targeting a lineage-specific PI3Kɣ-Akt signaling module in acute myeloid leukemia using a heterobifunctional degrader molecule.Nature cancer · 2024Article
- Metabolic modulation of histone acetylation mediated by HMGCL activates the FOXM1/β-catenin pathway in glioblastoma.Neuro-oncology · 2024Article
- Use of recombinant microRNAs as antimetabolites to inhibit human non-small cell lung cancer.Acta pharmaceutica Sinica. B · 2023Article
- Article
- Deacetylation of MTHFD2 by SIRT4 senses stress signal to inhibit cancer cell growth by remodeling folate metabolism.Journal of molecular cell biology · 2022Article
- P2RY2-AKT activation is a therapeutically actionable consequence of XPO1 inhibition in acute myeloid leukemia.Nature cancer · 2022Article
- Cystine uptake inhibition potentiates front-line therapies in acute myeloid leukemia.Leukemia · 2022Article
- Connections between metabolism and epigenetic modifications in cancer.Medical review (2021) · 2021Review
- The Role of Metabolism in the Development of Personalized Therapies in Acute Myeloid Leukemia.Frontiers in oncology · 2021Review
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Authors and funding
33 authors at 11 institutions in 4 countries.
Angela Su *INSERM UMR 944, IRSL, St Louis Hospital, University of Paris, Paris, France.
Frank Ling *INSERM UMR 944, IRSL, St Louis Hospital, University of Paris, Paris, France.
Camille VaganayINSERM UMR 944, IRSL, St Louis Hospital, University of Paris, Paris, France.
Gaetano SodaroINSERM UMR 944, IRSL, St Louis Hospital, University of Paris, Paris, France.ORCID https://orcid.org/0000-0002-7363-1124
Chaïma BenaksasINSERM UMR 944, IRSL, St Louis Hospital, University of Paris, Paris, France.
Reinaldo Dal BelloINSERM UMR 944, IRSL, St Louis Hospital, University of Paris, Paris, France.
Antoine ForgetINSERM UMR 944, IRSL, St Louis Hospital, University of Paris, Paris, France.
Bryann PardieuINSERM UMR 944, IRSL, St Louis Hospital, University of Paris, Paris, France.
Kevin H LinDepartment of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina.
Justine C RutterDepartment of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina.
Christopher F BassilDepartment of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina.
Gael FortinINSERM UMR 944, IRSL, St Louis Hospital, University of Paris, Paris, France.ORCID https://orcid.org/0000-0003-0461-1573
Justine PasanisiINSERM UMR 944, IRSL, St Louis Hospital, University of Paris, Paris, France.
Iléana Antony-DebréINSERM UMR 1287, Gustave Roussy Institute, Université Paris-Saclay, Villejuif, France.ORCID https://orcid.org/0000-0002-1911-146X
Gabriela AlexeDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.ORCID https://orcid.org/0000-0002-5668-6297
Jean-François BenoistAP-HP, Biochemistry-Hormonology Department, Robert Debré Hospital, Paris, France.
Alain PruvostParis-Saclay University, CEA, INRAE, Département Médicaments et Technologies pour la santé, SPI, Gif-sur-Yvette, France.ORCID https://orcid.org/0000-0002-7781-7735
Yana PikmanDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.ORCID https://orcid.org/0000-0002-5336-0216
Jun QiThe Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts.ORCID https://orcid.org/0000-0002-1461-3356
Marie-Hélène SchlageterAP-HP, Cellular Biology Department, St Louis Hospital, Paris, France.ORCID https://orcid.org/0000-0002-9507-0428
Jean-Baptiste MicolINSERM UMR 1287, Gustave Roussy Institute, Université Paris-Saclay, Villejuif, France.
Giovanni RotiUniversity of Parma, Department of Medicine and Surgery, Parma, Italy.
Thomas CluzeauDepartment of Hematology, Centre Hospitalier Universitaire, Nice, France.
Hervé DombretLTL, IRSL, St Louis Hospital, Paris, France.ORCID https://orcid.org/0000-0002-5454-6768
Claude PreudhommeLaboratory of Hematology, CHU Lille, Lille, France.
Nina FenouilleINSERM UMR 944, IRSL, St Louis Hospital, University of Paris, Paris, France.
Lina BenajibaINSERM UMR 944, IRSL, St Louis Hospital, University of Paris, Paris, France.
Hava M GolanZlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Kimberly StegmaierDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Camille Lobry *INSERM UMR 1287, Gustave Roussy Institute, Université Paris-Saclay, Villejuif, France.
Kris C Wood *Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina.ORCID https://orcid.org/0000-0002-5887-2253
Raphael Itzykson *INSERM UMR 944, IRSL, St Louis Hospital, University of Paris, Paris, France. alexandre.puissant@inserm.fr raphael.itzykson@aphp.fr.
Alexandre Puissant *INSERM UMR 944, IRSL, St Louis Hospital, University of Paris, Paris, France. alexandre.puissant@inserm.fr raphael.itzykson@aphp.fr.
Inserm · FRDuke University · USBroad Institute · USBen-Gurion University of the Negev · ILCentre Hospitalier Universitaire de Lille · FRCentre Hospitalier Universitaire de Nice · FRCommissariat à l'Énergie Atomique et aux Énergies Alternatives · FRDana-Farber Cancer Institute · USHôpital Robert-Debré · FRSaint Louis University Hospital · USUniversity of Parma · IT
Funding
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007171 · NIGMS · DUKE UNIVERSITY · PI KONTOS, CHRISTOPHER D · 1985 to 2021
$31.2MIntegrating Transforming Approaches to Identify and Target New Vulnerabilities in CancerR35CA210030 · NCI · DANA-FARBER CANCER INST · PI STEGMAIER, KIMBERLY · 2016 to 2022
$7.3MSelectively targeting apoptosis in PIK3CA mutant colorectal cancersR01CA207083 · NCI · DUKE UNIVERSITY · PI WOOD, KRIS C. · 2016 to 2020
$1.8MTargeting mitochondrial one carbon folate metabolism for novel T-cell acute lymphoblastic leukemia therapyK08CA222684 · NCI · DANA-FARBER CANCER INST · PI PIKMAN, YANA · 2018 to 2022
$886kEuropean Research Council 758848NCI NIH HHS K08 CA222684NCI NIH HHS R01 CA207083NCI NIH HHS R35 CA210030NIGMS NIH HHS T32 GM007171
Abstract
Deciphering the impact of metabolic intervention on response to anticancer therapy may elucidate a path toward improved clinical responses. Here, we identify amino acid-related pathways connected to the folate cycle whose activation predicts sensitivity to MYC-targeting therapies in acute myeloid leukemia (AML). We establish that folate restriction and deficiency of the rate-limiting folate cycle enzyme MTHFR, which exhibits reduced-function polymorphisms in about 10% of Caucasians, induce resistance to MYC targeting by BET and CDK7 inhibitors in cell lines, primary patient samples, and syngeneic mouse models of AML. Furthermore, this effect is abrogated by supplementation with the MTHFR enzymatic product CH
Indexed as
AnimalsClustered Regularly Interspaced Short Palindromic RepeatsDrug Resistance, NeoplasmFolic AcidHumansMaleMethylenetetrahydrofolate Reductase (NADPH2)MiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMolecular Targeted TherapyNeoplasmsProto-Oncogene Proteins c-mycU937 CellsFolic AcidMethylenetetrahydrofolate Reductase (NADPH2)MTHFR protein, humanMTHFR protein, mouseMYC protein, humanProto-Oncogene Proteins c-myc
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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.