ArticleCancer discovery2023
Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways.
Erratum issuedOpen access · hybridAbstract read
In one paragraph
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 108 papers.
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108citing papers in PubMed
38.8field-weighted citation impact, top 1% of its field
What it found
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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.
Who cites it
108 citing papers in PubMed, 135 citations in OpenAlex.
- Targeted therapies plus radiotherapy for diffuse intrinsic pontine glioma: the randomized phase 2 BIOMEDE trial.Nature medicine · 2026Trial
- A Phase 1 Randomized Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Escalating Oral Doses of Dordaviprone and the Effects of Food on the Bioavailability of Dordaviprone in Healthy Adult Subjects.Clinical pharmacology in drug development · 2025Trial
- ACTION: a randomized phase 3 study of ONC201 (dordaviprone) in patients with newly diagnosed H3 K27M-mutant diffuse glioma.Neuro-oncology · 2024Trial
- ONC201/dordaviprone for H3 K27M-mutant tumors: Discovery, mechanisms, therapeutic potential, and future directions.Genes & diseases · 2027Review
- The DIPG/DMG National Tumor Board: The power of advocacy.Neuro-oncology pediatrics · 2026Article
- Machine learning and computational approaches to model therapeutic response and resistance in diffuse midline glioma.Journal of neuro-oncology · 2026Review
- Oncohistone inhibition reshapes tumor-microenvironment communication in Diffuse Midline Glioma (DMG).bioRxiv : the preprint server for biology · 2026Article
- Single-nucleus profiling of postmortem diffuse midline gliomas identifies mitochondrial biogenesis as a resistance mechanism to imipridone therapy.Neuro-oncology · 2026Article
- Targeting ClpP Protease: Emerging Therapeutic Strategies and Small-Molecule Modulators in Drug Discovery.Medicinal research reviews · 2026Review
- Design, Synthesis, and Structure-Activity Relationships of Novel Piperidine-Fused Imidazolone ClpP Activators as Potential Anti-Cancer Agents.Molecules (Basel, Switzerland) · 2026Article
- Hippo pathway at the crossroads of stemness and therapeutic resistance in breast cancer.Molecular oncology · 2026Review
- ONC206 demonstrates potent antitumorigenic activity and is a potential novel therapeutic strategy for high-risk medulloblastoma.Neuro-oncology · 2026Article
- Combinatorial Targeting of Avapritinib-Driven MAP Kinase Activation in High-Grade Glioma.Research square · 2026Article
- Integrating Molecular Pathology, Tumor Microenvironment, and Novel Therapies to Overcome Resistance in Glioblastoma.Journal of molecular neuroscience : MN · 2026Review
- Tumor extracellular vesicle RNA profiling predicts treatment response in pediatric diffuse midline glioma.bioRxiv : the preprint server for biology · 2026Article
- Cerebrospinal Fluid in Pediatric Neuro-Oncology: Molecular Diagnosis, Disease Monitoring, and Clinical Translation.International journal of molecular sciences · 2026Review
- Harnessing the power of biomarkers for diffuse intrinsic pontine gliomas.Nature medicine · 2026Article
- Histone mark remodeling in cancer: an enhancer-centered perspective.Genes & genomics · 2026Review
- Re-evaluating the rationale for targeting oxidative phosphorylation in acute myeloid leukemia.The Biochemical journal · 2026Review
- Laser insterstitial thermal therapy followed by craniotomy for tumor resection for pediatric diffuse midline glioma: illustrative case.Journal of neurosurgery. Case lessons · 2026Article
48 more citing papers are in PubMed but not listed here.
Corrections and comments
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- Erratum issued
Authors and funding
84 authors at 20 institutions in 10 countries.
Sriram Venneti *University of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-9764-0423
Abed Rahman Kawakibi *University of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-6347-8974
Sunjong Ji *University of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-6516-2380
Sebastian M Waszak *University of California, San Francisco, San Francisco, California.ORCID 0000-0003-3042-9521
Stefan R Sweha *University of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-1807-6770
Mateus Mota *University of Michigan, Ann Arbor, Michigan.ORCID 0009-0006-3126-8212
Matthew Pun *University of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-4766-4301
Akash DeogharkarUniversity of Michigan, Ann Arbor, Michigan.ORCID 0009-0003-8980-0484
Chan ChungUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0003-0510-8996
Rohinton S TaraporeChimerix, Inc., Durham, North Carolina.ORCID 0000-0002-8070-5646
Samuel RamageChimerix, Inc., Durham, North Carolina.ORCID 0000-0002-0098-114X
Andrew ChiNYU Langone Health, New York, New York.ORCID 0000-0002-6642-1620
Patrick Y WenCenter for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.ORCID 0000-0002-0774-7700
Isabel Arrillaga-RomanyMassachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0001-5951-1225
Tracy T BatchelorBrigham and Women's Hospital, Boston, Massachusetts.ORCID 0000-0001-7568-6607
Nicholas A ButowskiUniversity of California, San Francisco, San Francisco, California.ORCID 0000-0001-5162-2406
Ashley SumrallLevine Cancer Institute, Charlotte, North Carolina.ORCID 0000-0002-2863-203X
Nicole ShonkaMayo Clinic, Rochester, Minnesota.ORCID 0000-0002-8182-3409
Rebecca A HarrisonBC Cancer, The University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0002-5689-8492
John de GrootUniversity of California, San Francisco, San Francisco, California.ORCID 0000-0003-1454-6461
Minesh MehtaMiami Cancer Institute, Miami, Florida.ORCID 0000-0002-4812-5713
Matthew D HallMiami Cancer Institute, Miami, Florida.ORCID 0000-0001-8768-3577
Doured DaghistaniMiami Cancer Institute, Miami, Florida.ORCID 0009-0007-2706-1611
Timothy F CloughesyUniversity of California, Los Angeles, Los Angeles, California.ORCID 0000-0002-8656-7483
Benjamin M EllingsonUniversity of California, Los Angeles, Los Angeles, California.ORCID 0000-0002-2764-6640
Kevin BeccariaDepartment of Neurosurgery, Necker Sick Children's University Hospital and Paris Descartes University, Paris, France.ORCID 0000-0002-3405-1944
Pascale VarletDepartment of Neuropathology, Sainte-Anne Hospital and Paris Descartes University, Paris, France.ORCID 0000-0002-8164-1517
Michelle M KimUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-7566-6411
Yoshie UmemuraUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-7137-661X
Hugh GartonUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-2573-2246
Andrea FransonUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-5361-7683
Jonathan SchwartzMayo Clinic, Rochester, Minnesota.ORCID 0000-0001-8965-6337
Rajan JainNYU Langone Health, New York, New York.ORCID 0000-0002-4879-0457
Maureen KachmanUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-9996-8446
Heidi BaumUniversity of Michigan, Ann Arbor, Michigan.ORCID 0009-0009-1504-5803
Charles F BurantUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-9189-5003
Sophie L MottlCentre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway.ORCID 0009-0005-4581-714X
Rodrigo T CartaxoUniversity of Michigan, Ann Arbor, Michigan.ORCID 0009-0001-2011-5695
Vishal JohnUniversity of Michigan, Ann Arbor, Michigan.ORCID 0009-0008-3218-0137
Dana MessingerUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-8421-0061
Tingting QinUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0003-3810-7578
Erik PetersonUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-6579-2948
Peter SajjakulnukitUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-8556-7481
Karthik RaviUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-9863-7736
Alyssa WaughUniversity of Michigan, Ann Arbor, Michigan.ORCID 0009-0001-0930-3142
Dustin WallingUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-2713-1196
Yujie DingUniversity of Michigan, Ann Arbor, Michigan.ORCID 0009-0007-2947-9296
Ziyun XiaUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-6409-1517
Anna SchwendemanUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-8023-8080
Debra HawesDepartment of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.ORCID 0000-0001-5936-4835
Fusheng YangDepartment of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.ORCID 0000-0002-8040-6312
Alexander R JudkinsDepartment of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.ORCID 0000-0002-9242-3769
Daniel WahlUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-9894-5085
Costas A LyssiotisUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-9309-6141
Daniel de la NavaHealth Research Institute of Navarra (IdiSNA), Pamplona, Spain.ORCID 0000-0003-0626-0711
Marta M AlonsoHealth Research Institute of Navarra (IdiSNA), Pamplona, Spain.ORCID 0000-0002-7520-7351
Augustine EzeCenter for Genetic Medicine Research, Children's National Hospital, Washington, DC.ORCID 0000-0001-6926-562X
Jasper SpitzerInstitute of Innate Immunity, AG Immunogenomics, University Hospital Bonn, Bonn, Germany.ORCID 0000-0001-9696-2092
Susanne V SchmidtInstitute of Innate Immunity, AG Immunogenomics, University Hospital Bonn, Bonn, Germany.ORCID 0000-0001-9561-2752
Ryan J DuchatelCancer Signalling Research Group, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia.ORCID 0000-0002-3651-7672
Matthew D DunCancer Signalling Research Group, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, Australia.ORCID 0000-0002-9063-5370
Jason E CainHudson Institute of Medical Research, Clayton, VIC, Australia.ORCID 0000-0003-3987-5894
Li JiangDepartment of Pediatric Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorder Center, Boston, Massachusetts.ORCID 0000-0001-7320-5283
Sylwia A StopkaDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.ORCID 0000-0003-3761-6899
Gerard BaquerDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-4433-4972
Michael S ReganDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-5252-2829
Mariella G FilbinDepartment of Pediatric Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorder Center, Boston, Massachusetts.ORCID 0000-0002-2613-8126
Nathalie Y R AgarDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.ORCID 0000-0003-3149-3146
Lili ZhaoUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-6366-8206
Chandan Kumar-SinhaUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-8696-3400
Rajen ModyUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-5574-1779
Arul ChinnaiyanUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-9282-3415
Ryo KurokawaUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-1186-8900
Drew PrattLaboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.ORCID 0000-0003-3583-8308
Viveka N YadavDepartment of Pediatrics at Children's Mercy Research Institute, Kansas City, Missouri.ORCID 0009-0001-5354-3717
Jacques GrillDepartment of Pediatric and Adolescent Oncology and INSERM Unit 981, Gustave Roussy and University Paris-Saclay, Villejuif, France.ORCID 0000-0003-4773-3001
Cassie KlineDivision of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.ORCID 0000-0001-7765-7690
Sabine MuellerUniversity of California, San Francisco, San Francisco, California.ORCID 0000-0002-3452-5150
Adam ResnickDivision of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.ORCID 0000-0003-0436-4189
Javad NazarianDepartment of Pediatrics, Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.ORCID 0000-0002-1951-9828
Joshua E AllenChimerix, Inc., Durham, North Carolina.ORCID 0000-0002-6835-1128
Yazmin OdiaMiami Cancer Institute, Miami, Florida.ORCID 0000-0003-3602-3899
Sharon L GardnerNYU Langone Health, New York, New York.ORCID 0000-0002-8857-5487
Carl KoschmannUniversity of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-0825-7615
University of Michigan · USBrigham and Women's Hospital · USChildren's Hospital of Los Angeles · USNYU Langone Health · USBoston Medical Center · USCancer Institute of Florida · USChildren's Hospital of Philadelphia · USChildren's National · USChimerix (United States) · USHunter Medical Research Institute · AUMayo Clinic · USNavarre Institute of Health Research · ESOslo University Hospital · NOUniversity Hospital Bonn · DEUniversity of California, Los Angeles · USUniversity of California, San Francisco · USArgos Therapeutics (United States) · USBaptist Hospital of Miami · USDaegu Gyeongbuk Institute of Science and Technology · KRDana-Farber Brigham Cancer Center · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MXenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2MMICHIGAN MEDICAL SCIENTIST TRAINING PROGRAMT32GM007863 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 1985 to 2024
$38.3MUCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2MPilot and Feasibility (P and F) ProgramP30DK089503 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Kanakadurga Singer · 2010 to 2026
$20.3MStatistics and Bioinformatics Core - WangU24DK097153 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BURANT, CHARLES F · 2012 to 2017
$10.1MSequencing, Analysis, and Interpretation of SequencingUM1HG006508 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PIENTA, KENNETH J., PIENTA, KENNETH J. · 2013 to 2016
$7.8MClinical efficacy of the antitumor agent ONC201 in GBMR44CA192427 · NCI · ONCOCEUTICS, INC. · PI ALLEN, JOSHUA E. · 2015 to 2020
$4.8MRole of decorin and diffusion MRI in anti-VEGF efficacy for recurrent glioblastomaR01CA270027 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TIMOTHY CLOUGHESY, Benjamin M. Ellingson · 2022 to 2026
$3.0MTargeting integrated metabolic and epigenetic pathways in childhood ependymomasR01CA261926 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Deepak Nagrath, Benita Tamrazi · 2022 to 2026
$3.0MUnravelling metabolic dependencies in H3K27M mutant DIPGR01NS110572 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sriram Venneti · 2019 to 2026
$2.7MQuantitative molecular MR-PET imaging of glycolysis in glioblastomaR01CA279984 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Benjamin M. Ellingson, David A. Nathanson · 2023 to 2026
$2.4MNCI NIH HHS P30 CA008748NCI NIH HHS P30 CA046592NCI NIH HHS P50 CA211015NCI NIH HHS R01 CA261926NCI NIH HHS R01 CA270027NCI NIH HHS R01 CA279984NCI NIH HHS R44 CA192427NHGRI NIH HHS UM1 HG006508NIDDK NIH HHS P30 DK089503NIDDK NIH HHS U24 DK097153NIGMS NIH HHS T32 GM007863NINDS NIH HHS R01 NS110572NINDS NIH HHS R01 NS119231NINDS NIH HHS R01 NS124607NINDS NIH HHS R01 NS127799
Abstract
Patients with H3K27M-mutant diffuse midline glioma (DMG) have no proven effective therapies. ONC201 has recently demonstrated efficacy in these patients, but the mechanism behind this finding remains unknown. We assessed clinical outcomes, tumor sequencing, and tissue/cerebrospinal fluid (CSF) correlate samples from patients treated in two completed multisite clinical studies. Patients treated with ONC201 following initial radiation but prior to recurrence demonstrated a median overall survival of 21.7 months, whereas those treated after recurrence had a median overall survival of 9.3 months. Radiographic response was associated with increased expression of key tricarboxylic acid cycle-related genes in baseline tumor sequencing. ONC201 treatment increased 2-hydroxyglutarate levels in cultured H3K27M-DMG cells and patient CSF samples. This corresponded with increases in repressive H3K27me3 in vitro and in human tumors accompanied by epigenetic downregulation of cell cycle regulation and neuroglial differentiation genes. Overall, ONC201 demonstrates efficacy in H3K27M-DMG by disrupting integrated metabolic and epigenetic pathways and reversing pathognomonic H3K27me3 reduction. SIGNIFICANCE: The clinical, radiographic, and molecular analyses included in this study demonstrate the efficacy of ONC201 in H3K27M-mutant DMG and support ONC201 as the first monotherapy to improve outcomes in H3K27M-mutant DMG beyond radiation. Mechanistically, ONC201 disrupts integrated metabolic and epigenetic pathways and reverses pathognomonic H3K27me3 reduction. This article is featured in Selected Articles from This Issue, p. 2293.
Indexed as
Brain NeoplasmsGliomaEpigenesis, GeneticHistonesHumansImidazolesMutationPyridinesPyrimidinesTreatment OutcomeHistonesImidazolesPyridinesPyrimidinesTIC10 compound
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