Evidence map›Paper›PMID 42760279›Full record

ArticleNature communications2026

Autophagy inhibition sensitizes radiotherapy responses in high-grade mutant IDH1 glioma.

Felipe J Núñez, Kaushik Banerjee, Anzar A Mujeeb, Ava Mauser, Claire E Tronrud, Ziwen Zhu, Sadhakshi Raghuram, Maya R Sheth, Jorge Armando Pena Agudelo, Julio Zelaya and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors.

Felipe J Núñez *Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Kaushik Banerjee *Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Anzar A Mujeeb *Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Ava Mauser *Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA.
Claire E Tronrud *Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Ziwen Zhu *Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-6681-9153
Sadhakshi RaghuramDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Maya R ShethDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Jorge Armando Pena AgudeloDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Julio ZelayaDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA.
Ayman TaherDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Padma KadiyalaDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Stephen V CarneyDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Maria B Garcia-FabianiDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Andrea CombaDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-3398-5753
Mahmoud S AlghamriDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Brandon L McClellanDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Adam KlaissDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID http://orcid.org/0009-0008-5588-900X
Zeribe C NwosuRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0003-1641-2045
Hanna S HongRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Peter SajjakulnukitDepartment of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-8556-7481
Tingting QinDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
Maureen A SartorDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-6155-5702
Mats LjungmanDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0003-1553-6695
Joshua D WelchDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-5869-2391
Shi-Yuan ChengKen & Ruth Davee Department of Neurology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0003-1737-0588
Pedro R LowensteinDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-8427-4409
Joerg LahannDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA. lahann@umich.edu.ORCID http://orcid.org/0000-0002-3334-2053
Costas A LyssiotisRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA. clyssiot@umich.edu.
Maria G CastroDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA. mariacas@umich.edu.ORCID http://orcid.org/0000-0003-2237-2756

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Eric R. Fearon · 1988 to 2026
$178.2M
3-D spatial approach to discover genomic effectors of immunosuppression during malignant transformationR01CA244838 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COSTELLO, JOSEPH F · 2020 to 2024
$2.7M
Systemic Delivery of Targeted Bi-Compartmental Nanoparticles for Glioblastoma Therapeutics (Supplement)R01NS124167 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Maria G Castro, JOERG LAHANN · 2022 to 2026
$2.6M
Uncover the role of H3.3-G343R mutation in shaping the DNA damage response, anti-tumor immunity and mechanisms of resistance in glioma.R01NS122165 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Maria G Castro · 2022 to 2026
$2.5M
The Role of Collagen and its Signaling Mechanisms in Glioma Progression and Invasion.R01NS122234 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Pedro R. Lowenstein · 2022 to 2026
$2.4M
Stromal metabolism promotes therapeutic resistance in pancreatic cancerR01CA248160 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LYSSIOTIS, COSTAS ANDREAS · 2020 to 2024
$2.0M
Targeting metabolic stress to induce pancreatic tumor cell deathR01CA244931 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LYSSIOTIS, COSTAS ANDREAS · 2020 to 2024
$1.9M
Chemo-immunotherapy strategy for pediatric high grade gliomaR21NS123879 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CASTRO, MARIA G, SCHWENDEMAN, ANNA · 2021 to 2021
$429k
NCI NIH HHS P30 CA046592NCI NIH HHS R01 CA244838NCI NIH HHS R01 CA244931NCI NIH HHS R01 CA248160NINDS NIH HHS R01 NS122165NINDS NIH HHS R01 NS122234NINDS NIH HHS R01 NS124167NINDS NIH HHS R21 NS123879U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 2P30CA46592U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA244931U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA248160U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01-NS122165U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01NS122234U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01-NS122378U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01-NS124167U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R21-NS123879-01
6 · The paper itself

Abstract

Mutant isocitrate dehydrogenase 1 (mIDH1) catalyzes 2-hydroxyglutarate (2HG) production which leads to epigenetic reprogramming in astrocytomas with tumor protein p53 (TP53)/α-thalassemia/mental retardation, X-linked (ATRX) loss. RNA-sequencing, single-cell RNA-sequencing, and Chromatin Immunoprecipitation sequencing (ChIP-seq) followed by bioinformatics analysis shows that human and mouse mIDH1 gliomas exhibit downregulated gene ontologies (GOs) related to mitochondrial metabolism and upregulated autophagy-related GOs. Decreased mitochondrial metabolism is accompanied by decreased glycolysis, rendering autophagy as a source of energy in mIDH1 gliomas. Mutant IDH1 glioma cells exhibit increased expression of autophagy-related proteins and enhanced microtubule-associated protein 1 light chain 3 (LC3) I/II conversion, indicating augmented autophagy. Inhibiting autophagy in vivo by administration of synthetic protein nanoparticles (SPNPs) encapsulating autophagy related gene 7 (ATG7) silencing RNA sensitizes mIDH1 glioma cells to radiation, resulting in tumor regression, long-term survival, and immunological memory. This work uncovers autophagy as a critical pathway for survival in mIDH1 gliomas and its inhibition elicits radiosensitivity in vitro in human and mouse mIDH1 glioma cells, and in vivo in mIDH1 models.

Indexed as

AutophagyBrain NeoplasmsGliomaIsocitrate DehydrogenaseRadiation ToleranceAnimalsAutophagy-Related Protein 7Cell Line, TumorGene Expression Regulation, NeoplasticHumansMiceMicrotubule-Associated ProteinsMitochondriaMutationATG7 protein, humanAutophagy-Related Protein 7IDH1 protein, humanIdh1 protein, mouseIsocitrate DehydrogenaseMicrotubule-Associated Proteins

Identifiers

PMID42760279
PMCPMC13588786

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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.