Evidence map›Paper›PMID 37279645›Full record

ArticleNeuro-oncology2023

M2 isoform of pyruvate kinase rewires glucose metabolism during radiation therapy to promote an antioxidant response and glioblastoma radioresistance.

Justine Bailleul, Yangjingyi Ruan, Lobna Abdulrahman, Andrew J Scott, Taha Yazal, David Sung, Keunseok Park, Hanna Hoang, Juan Nathaniel, Fang-I Chu and 15 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
5.5field-weighted citation impact, top 4% of its field
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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Hyperpolarized MRI theranostics in cancer.Frontiers in oncology · 2025
    Article
  17. Review
  18. Review
  19. Review
  20. Review
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

25 authors at 2 institutions in 1 country.

Justine BailleulDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.ORCID 0000-0002-3974-1928
Yangjingyi RuanDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Lobna AbdulrahmanDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Andrew J ScottDepartment of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA.
Taha YazalDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
David SungDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Keunseok ParkDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California, USA.
Hanna HoangDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Juan NathanielDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Fang-I ChuDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Daisy PalomeraDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Anahita SehgalDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Jonathan E TsangDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
David A NathansonDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Shili XuJonsson Comprehensive Cancer Center, University of California, Los Angeles, California, USA.
Junyoung O ParkDepartment of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California, USA.
Johanna Ten HoeveDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Kruttika BhatDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Nathan QiDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
Harley I KornblumJonsson Comprehensive Cancer Center, University of California, Los Angeles, California, USA.
Dorthe SchaueDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
William H McBrideDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Costas A LyssiotisDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
Daniel R WahlDepartment of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA.
Erina VlashiDepartment of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.ORCID 0000-0002-2505-3577
University of California, Los Angeles · USUniversity of Michigan · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2M
Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2M
Michigan Mouse Metabolic Phenotyping CenterU2CDK110768 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ELIAS, CAROL FUZETI · 2016 to 2021
$6.2M
Targeting Nucleotide Metabolism to Overcome Therapy Resistance in GlioblastomaR37CA258346 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Daniel R Wahl · 2021 to 2026
$3.3M
Drivers of Metabolic Plasticity Promote Radiation Resistance in Glioblastoma MultiformeR01CA251872 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI VLASHI, ERINA · 2020 to 2024
$2.8M
Molecular basis linking metabolic heterogeneity, compatibility, and adaptabilityR35GM143127 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Junyoung O. Park · 2021 to 2026
$2.5M
Radiation-induced vascular reprogramming in glioblastomaR01NS121617 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HARLEY IAN KORNBLUM · 2022 to 2026
$2.3M
De Novo Nucleotide Synthesis as a Mediator of Radiation Resistance and a Therapeutic Target in GlioblastomaK08CA234416 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WAHL, DANIEL R · 2019 to 2023
$1.1M
Targeting purine biosynthesis to radiosensitize glioblastomaF32CA260735 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SCOTT, ANDREW JOSEPH · 2021 to 2023
$185k
NCATS NIH HHS UL1 TR001881NCI NIH HHS F32 CA260735NCI NIH HHS K08 CA234416NCI NIH HHS K08CA234416NCI NIH HHS P30 CA016042NCI NIH HHS P30 CA046592NCI NIH HHS P50 CA211015NCI NIH HHS R01 CA251872NCI NIH HHS R37 CA258346NIDDK NIH HHS U2C DK110768NIGMS NIH HHS R35 GM143127NINDS NIH HHS R01 NS121617
6 · The paper itself

Abstract

backgroundResistance to existing therapies is a significant challenge in improving outcomes for glioblastoma (GBM) patients. Metabolic plasticity has emerged as an important contributor to therapy resistance, including radiation therapy (RT). Here, we investigated how GBM cells reprogram their glucose metabolism in response to RT to promote radiation resistance.

methodsEffects of radiation on glucose metabolism of human GBM specimens were examined in vitro and in vivo with the use of metabolic and enzymatic assays, targeted metabolomics, and FDG-PET. Radiosensitization potential of interfering with M2 isoform of pyruvate kinase (PKM2) activity was tested via gliomasphere formation assays and in vivo human GBM models.

resultsHere, we show that RT induces increased glucose utilization by GBM cells, and this is accompanied with translocation of GLUT3 transporters to the cell membrane. Irradiated GBM cells route glucose carbons through the pentose phosphate pathway (PPP) to harness the antioxidant power of the PPP and support survival after radiation. This response is regulated in part by the PKM2. Activators of PKM2 can antagonize the radiation-induced rewiring of glucose metabolism and radiosensitize GBM cells in vitro and in vivo.

conclusionsThese findings open the possibility that interventions designed to target cancer-specific regulators of metabolic plasticity, such as PKM2, rather than specific metabolic pathways, have the potential to improve the radiotherapeutic outcomes in GBM patients.

Indexed as

GlioblastomaPyruvate KinaseAntioxidantsCell Line, TumorGlucoseHumansProtein IsoformsAntioxidantsGlucoseProtein IsoformsPyruvate KinaseglioblastomametabolismplasticityPPPradiation resistance

Identifiers

PMID37279645
PMCPMC10628945
OpenAlexW4379598192

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.