Evidence map›Paper›PMID 39394920›Full record

ArticleNeuro-oncology2025

Targeted delivery of napabucasin with radiotherapy improves outcomes in diffuse midline glioma.

Matthew Gallitto, Xu Zhang, Genesis De Los Santos, Hong-Jian Wei, Ester Calvo Fernández, Shoufu Duan, Geoffrey Sedor, Nina Yoh, Danae Kokossis, J Carlos Angel and 19 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Local delivery of interferon restores antigen presentation and sensitizes medulloblastoma to T cell killing.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Article
  3. Review
  4. Review
  5. Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025
    Review
  6. Article
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

29 authors.

Matthew GallittoHerbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian, New York, New York, USA.ORCID 0000-0002-5210-742X
Xu ZhangDepartment of Genetics and Development, Institute for Cancer Genetics, Columbia University Irving Medical Center, New York, New York, USA.
Genesis De Los SantosDepartment of Radiation Oncology, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian, New York, New York, USA.
Hong-Jian WeiFralin Biomedical Research Institute, Virginia Polytechnic Institute and State University, Roanoke, 24016, USA.
Ester Calvo FernándezDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.
Shoufu DuanDepartment of Genetics and Development, Institute for Cancer Genetics, Columbia University Irving Medical Center, New York, New York, USA.
Geoffrey SedorHerbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian, New York, New York, USA.
Nina YohDepartment of Neurological Surgery, Columbia University Irving Medical Center, New York, New York, USA.
Danae KokossisDepartment of Radiation Oncology, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian, New York, New York, USA.
J Carlos AngelDepartment of Molecular Pharmacology and Therapeutics, Columbia University, New York, New York, USA.
Yi-Fang WangDepartment of Radiation Oncology, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian, New York, New York, USA.
Erin WhiteDepartment of Systems Biology, Columbia University Irving Medical Center, New York, New York, USA.
Connor J KinslowHerbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian, New York, New York, USA.
Xander BergDepartment of Radiation Oncology, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian, New York, New York, USA.
Lorenzo TomassoniDepartment of Systems Biology, Columbia University Irving Medical Center, New York, New York, USA.
Fereshteh ZandkarimiDepartment of Chemistry, Columbia University, New York, New York, USA.
Iok In Christine ChioDepartment of Genetics and Development, Institute for Cancer Genetics, Columbia University Irving Medical Center, New York, New York, USA.
Peter CanollDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.
Jeffrey N BruceDepartment of Neurological Surgery, Columbia University Irving Medical Center, New York, New York, USA.
Neil A FeldsteinDepartment of Neurological Surgery, Columbia University Irving Medical Center, New York, New York, USA.
Robyn D GartrellDepartment of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA.
Simon K ChengHerbert Irving Comprehensive Cancer Center, Columbia University Vagelos College of Physicians and Surgeons and NewYork-Presbyterian, New York, New York, USA.
James H GarvinDepartment of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA.
Stergios ZacharoulisDepartment of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA.
Robert J Wechsler-ReyaDepartment of Neurology, Columbia University Irving Medical Center, New York, New York, USA.
Jovana PavisicDepartment of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA.
Andrea CalifanoChan Zuckerberg Biohub New York, New York, New York, USA.
Zhiguo ZhangDepartment of Genetics and Development, Institute for Cancer Genetics, Columbia University Irving Medical Center, New York, New York, USA.ORCID 0000-0002-9451-2685
Cheng-Chia WuFralin Biomedical Research Institute, Virginia Polytechnic Institute and State University, Roanoke, 24016, USA.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Predicting Cancer Cell Response to Endogenous and Exogenous Perturbations at the Single Cell LevelR35CA197745 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ANDREA CALIFANO · 2015 to 2026
$11.5M
Elucidating and Targeting tumor dependencies and drug resistance determinants at the single cell levelU01CA272610 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ANDREA CALIFANO · 2022 to 2026
$4.8M
Identifying and Targeting the Drivers of Pediatric Brain TumorsR35NS122339 · NINDS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Robert J. Wechsler-Reya · 2021 to 2026
$3.6M
High-performance compute cluster for biomedical computingS10OD012351 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2012 to 2012
$2.0M
High Performance Computing Cluster for Biomedical ResearchS10OD032433 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2023 to 2023
$2.0M
Roles of Chromatin Remodeler CHD2 in Diffuse Midline Glioma with Onco-Histone MutationsR01NS132344 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Zhiguo Zhang · 2023 to 2026
$1.8M
Epigenetic dependence of diffuse midline glioma with H3K27M mutationR01CA277605 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Zhiguo Zhang · 2023 to 2026
$1.8M
CAPRI: Columbia Cancer Research Training Program for Resident-InvestigatorsR38CA277850 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Katherine D Crew, Lisa A. Kachnic · 2024 to 2026
$1.6M
Storage System for High Performance ComputingS10OD021764 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2016 to 2016
$600k
American Society of Clinical OncologyNCI NIH HHS P30 CA008748NCI NIH HHS R01 CA277605NCI NIH HHS R35 CA197745NCI NIH HHS R38 CA277850NCI NIH HHS U01 CA272610NIH HHS S10 OD012351NIH HHS S10 OD021764NIH HHS S10 OD032433NINDS NIH HHS R01 NS132344NINDS NIH HHS R35 NS122339Radiological Society of North America
6 · The paper itself

Abstract

backgroundDiffuse midline glioma (DMG) is the most aggressive primary brain tumor in children. All previous studies examining the role of systemic agents have failed to demonstrate a survival benefit; the only standard of care is radiation therapy (RT). Successful implementation of radiosensitization strategies in DMG remains an essential and promising avenue of investigation. We explore the use of Napabucasin, an NAD(P)H quinone dehydrogenase 1 (NQO1)-bioactivatable reactive oxygen species (ROS)-inducer, as a potential therapeutic radiosensitizer in DMG.

methodsIn this study, we conduct in vitro and in vivo assays using patient-derived DMG cultures to elucidate the mechanism of action of Napabucasin and its radiosensitizing properties. As penetration of systemic therapy through the blood-brain barrier (BBB) is a significant limitation to the success of DMG therapies, we explore focused ultrasound (FUS) and convection-enhanced delivery (CED) to overcome the BBB and maximize therapeutic efficacy.

resultsNapabucasin is a potent ROS-inducer and radiosensitizer in DMG, and treatment-mediated ROS production and cytotoxicity are dependent on NQO1. In subcutaneous xenograft models, combination therapy with RT improves local control. After optimizing targeted drug delivery using CED in an orthotopic mouse model, we establish the novel feasibility and survival benefit of CED of Napabucasin concurrent with RT.

conclusionsAs nearly all DMG patients will receive RT as part of their treatment course, our validation of the efficacy of radiosensitizing therapy using CED to prolong survival in DMG opens the door for exciting novel studies of alternative radiosensitization strategies in this devastating disease while overcoming limitations of the BBB.

Indexed as

Brain NeoplasmsChemoradiotherapyDrug Delivery SystemsGliomaNaphthoquinonesRadiation-Sensitizing AgentsAnimalsBenzofuransBlood-Brain BarrierFemaleHumansMiceMice, NudeReactive Oxygen SpeciesTumor Cells, CulturedXenograft Model Antitumor AssaysBenzofuransnapabucasinNaphthoquinonesRadiation-Sensitizing AgentsReactive Oxygen Speciesblood-brain barrierconvection-enhanced drug deliverydiffuse midline gliomafocused ultrasoundradiosensitization

Identifiers

PMID39394920
PMCPMC11889722

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.