ArticleCancer cell2024
Mutant IDH inhibitors induce lineage differentiation in IDH-mutant oligodendroglioma.
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Article in Cancer cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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45 citing papers in PubMed.
- Article
- Article
- Gliomas phenocopy an inborn error of metabolism to drive neuronal activity and tumor growth.Cell · 2026Article
- A single-cell lens into the co-evolution of genotypes and phenotypes in cancer.Nature reviews. Cancer · 2026Review
- The critical role of the endogenous immune compartment after CAR T cell therapy in recurrent GBM.Cell · 2026Article
- Vorasidenib improves response to subsequent chemoradiation in a genetically engineered mouse model of IDH-mutant glioma.Science translational medicine · 2026Article
- Longitudinal changes in DNA methylation in IDH-mutant glioma fuel disease progression through altered cell state differentiation.Nature genetics · 2026Article
- Article
- Kinsenoside Targets IDH1 to Restore Microglial Immune-Metabolic Homeostasis for Alzheimer's Disease Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Notch Overexpression Potentiates Interferon Signaling in Glioma Cells.Current issues in molecular biology · 2026Article
- A longitudinal single-cell and spatial multiomic atlas of pediatric high-grade glioma.Cell reports. Medicine · 2026Article
- Murine modeling of IDH-mutant 1p/19q-codeleted oligodendroglioma reveals genotype specific phenotypes.bioRxiv : the preprint server for biology · 2026Article
- From Epigenetic Constraint to Evolutionary Escape: Cell-State Transitions and Selective Pressures During Malignant Transformation in Lower-Grade Gliomas.Biomedicines · 2026Review
- Distinct molecular profiles characterize the spontaneous growth rate of IDHmt low-grade astrocytomas and oligodendrogliomas.Neuro-oncology · 2026Article
- Single-nucleus transcriptomics, pharmacokinetics, and pharmacodynamics of CDK4/6 and mTOR inhibition in a Phase 0/1 trial of recurrent high-grade glioma.Neuro-oncology · 2026Article
- Reasons driving choice and clinical course of patients with CNS WHO grade 3 IDH mutant glioma receiving vorasidenib after surgery: a pilot experience.Journal of neuro-oncology · 2026Article
- Current Pharmacotherapeutic Strategies in Diffuse Gliomas: Focus on Glioblastoma, IDH-Wildtype, and Emerging Targeted Therapies for IDH-Mutant Tumors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Network-Based Prediction of Oligodendroglioma Driver Gene Candidates within the Region of the 1p/19q Co-deletion Utilizing Single-Cell Transcriptomes.Computational and structural biotechnology journal · 2026Article
- Mitochondrial transfer-mediated metabolic reprogramming and drug resistance in bone metastasis: mechanisms and therapeutic strategies.Frontiers in immunology · 2026Review
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Authors and funding
30 authors.
Avishay SpitzerDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 761001, Israel; Department of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Simon GritschDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Masashi NomuraDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Alexander JuchtDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Jerome FortinPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada; Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Montreal, Canada.
Ramya RaviramNew York Genome Center, New York, NY, USA; Weill Cornell Medicine, New York, NY, USA.
Hannah R WeismanDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
L Nicolas Gonzalez CastroDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Center for Neuro-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Nicholas DruckDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Rony Chanoch-MyersDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 761001, Israel.
John J Y LeeDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Ravindra MylvaganamDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Rachel Lee ServisDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Jeremy Man FungDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Christine K LeeDepartment of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Hiroaki NagashimaDepartment of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Julie J MillerPappas Center for Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Isabel Arrillaga-RomanyDepartments of Neurology and Radiation Oncology, Division of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
David N LouisDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Hiroaki WakimotoDepartment of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Will PisanoDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Patrick Y WenCenter for Neuro-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Tak W MakPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada; Centre for Oncology and Immunology, Hong Kong Science Park, Hong Kong SAR, China; Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Marc SansonSorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Paris, France.
Mehdi TouatSorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Paris, France; Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Dan A LandauNew York Genome Center, New York, NY, USA; Weill Cornell Medicine, New York, NY, USA.
Keith L LigonBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA; Department of Pathology, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: keith_ligon@dfci.harvard.edu.
Daniel P CahillDepartment of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: cahill@mgh.harvard.edu.
Mario L SuvàDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: suva.mario@mgh.harvard.edu.
Itay TiroshDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 761001, Israel. Electronic address: itay.tirosh@weizmann.ac.il.
Funding
Targeting the Vasular SystemP50CA165962 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI WENDY Beth LONDON · 2013 to 2026
$33.5MGenetic evolution of glioblastomas during radiation and temozolomide therapyR01CA188228 · NCI · DANA-FARBER CANCER INST · PI BEROUKHIM, RAMEEN, CHAKRAVARTI, ARNAB · 2015 to 2025
$6.9MTargeting the neuronal microenvironment in glioblastomaU19CA264504 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Tracy T Batchelor · 2021 to 2026
$6.4MDissecting the cellular hierarchies of malignant gliomas by single-cell functional genomicsR37CA245523 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Mario Luca Suva · 2020 to 2026
$2.8MDeciphering heritability, plasticity and differentiation trajectories in gliomas via single-cell multi-omicsR01CA258763 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI SUVA, MARIO LUCA · 2021 to 2025
$2.8MDissecting the Determinants of IDH-mutant Gliomas Response to Mutant IDH InhibitorsR01CA276765 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel P. Cahill, Mario Luca Suva · 2023 to 2026
$2.7MNCI NIH HHS P50 CA165962NCI NIH HHS R01 CA188228NCI NIH HHS R01 CA258763NCI NIH HHS R01 CA276765NCI NIH HHS R37 CA245523NCI NIH HHS U19 CA264504
Abstract
A subset of patients with IDH-mutant glioma respond to inhibitors of mutant IDH (IDHi), yet the molecular underpinnings of such responses are not understood. Here, we profiled by single-cell or single-nucleus RNA-sequencing three IDH-mutant oligodendrogliomas from patients who derived clinical benefit from IDHi. Importantly, the tissues were sampled on-drug, four weeks from treatment initiation. We further integrate our findings with analysis of single-cell and bulk transcriptomes from independent cohorts and experimental models. We find that IDHi treatment induces a robust differentiation toward the astrocytic lineage, accompanied by a depletion of stem-like cells and a reduction of cell proliferation. Furthermore, mutations in NOTCH1 are associated with decreased astrocytic differentiation and may limit the response to IDHi. Our study highlights the differentiating potential of IDHi on the cellular hierarchies that drive oligodendrogliomas and suggests a genetic modifier that may improve patient stratification.
Indexed as
Brain NeoplasmsCell DifferentiationIsocitrate DehydrogenaseMutationOligodendrogliomaAnimalsAstrocytesCell LineageCell ProliferationHumansMiceReceptor, Notch1Single-Cell AnalysisIsocitrate DehydrogenaseReceptor, Notch1differentiation therapygliomaIDH1ivosideniboligodendrogliomasingle cell RNA-seqvorasidenib
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