Evidence map›Paper›PMID 40009641›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Radiation-induced cellular plasticity primes glioblastoma for forskolin-mediated differentiation.

Ling He, Daria Azizad, Kruttika Bhat, Angeliki Ioannidis, Carter J Hoffmann, Evelyn Arambula, Mansoureh Eghbali, Aparna Bhaduri, Harley I Kornblum, Frank Pajonk

Erratum issuedAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. 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 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Review
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  8. Radiation-induced cellular plasticity primes glioblastoma for forskolin-mediated differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Ling HeDepartment of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles, CA 90095.ORCID 0000-0002-8692-7530
Daria AzizadDepartment of Biological Chemistry at University of California, Los Angeles, CA 90095.ORCID 0009-0006-7015-9027
Kruttika BhatDepartment of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles, CA 90095.
Angeliki IoannidisDepartment of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles, CA 90095.ORCID 0000-0002-2956-3304
Carter J HoffmannDepartment of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles, CA 90095.
Evelyn ArambulaDepartment of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles, CA 90095.
Mansoureh EghbaliDepartment of Anesthesiology at University of California, Los Angeles, CA 90095.
Aparna BhaduriJonsson Comprehensive Cancer Center at University of California, Los Angeles, CA 90095.ORCID 0000-0003-4625-6899
Harley I KornblumJonsson Comprehensive Cancer Center at University of California, Los Angeles, CA 90095.ORCID 0000-0002-3779-4540
Frank PajonkDepartment of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles, CA 90095.ORCID 0000-0003-4067-9751

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Robert Damoiseaux · 1985 to 2026
$134.5M
Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2M
Shared Resource Core: Single Cell AnalysisU54CA217378 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI LANDER, ARTHUR D · 2018 to 2022
$9.7M
UCLA IDDRC: Translational CoreP50HD103557 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Peyman Golshani, SUMA JACOB · 2020 to 2026
$9.6M
UCI P30 Skin Center Systems Biology CoreP30AR075047 · NIAMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI ANDERSEN, BOGI, GANESAN, ANAND K · 2019 to 2025
$5.1M
Use of CTEP portfolio compounds to counteract phenotype conversion in GBMR01CA260886 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Frank Pajonk · 2022 to 2026
$2.6M
Utilizing Radiation-Induced Multi-potency to Increase the Efficacy of RadiotherapyR01CA281682 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Frank Pajonk · 2023 to 2026
$2.0M
PacBio RS Single Molecule, Real-Time (SMRT) DNA SequencerS10OD010794 · OD · UNIVERSITY OF CALIFORNIA-IRVINE · PI SANDMEYER, SUZANNE · 2012 to 2012
$600k
High-Throughput DNA SequencerS10OD021718 · OD · UNIVERSITY OF CALIFORNIA-IRVINE · PI SANDMEYER, SUZANNE · 2016 to 2016
$600k
High Throughput DNA SequencerS10RR025496 · NCRR · UNIVERSITY OF CALIFORNIA-IRVINE · PI SANDMEYER, SUZANNE · 2009 to 2009
$500k
Human brain organoids as a novel platform for evaluating effects of radiation in the CNS and screening for radiation mitigatorsR03CA289852 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HE, LING · 2024 to 2025
$157k
NCI NIH HHS P30 CA016042NCI NIH HHS P30 CA062203NCI NIH HHS P50 CA211015NCI NIH HHS R01 CA260886NCI NIH HHS R01 CA281682NCI NIH HHS R03 CA289852NCI NIH HHS U54 CA217378NCRR NIH HHS S10 RR025496NIAMS NIH HHS P30 AR075047NICHD NIH HHS P50 HD103557NIH HHS S10 OD010794NIH HHS S10 OD021718NIH/NCI R01CA260886NIH/NCI R01CA281682
6 · The paper itself

Abstract

Glioblastoma (GBM) is the deadliest brain cancer in adults, and all patients succumb to the tumor. While surgery followed by chemoradiotherapy delays disease progression, these treatments do not lead to tumor control, and targeted therapies or biologics have failed to further improve survival. Utilizing a transient radiation-induced state of multipotency, we used the adenylcyclase activator forskolin to alter the fate of irradiated glioma cells. The effects of the combined treatment on neuronal marker expression, cell cycle distribution, and proliferation were studied. Gene expression profiling was conducted using bulk RNA-seq. Changes in cell populations were investigated using single-cell RNA-seq. Effects on glioma stem cells (GSCs) were studied in extreme limiting dilution assays, and the effects on median survival were studied in both syngeneic and PDOX mouse models of GBM. The combined treatment induced the expression of neuronal markers in glioma cells, reduced proliferation, and led to a distinct gene expression profile. scRNA-seq revealed that the combined treatment forced glioma cells into a microglia- and neuron-like phenotype. In vivo, this treatment led to a loss of GSCs and prolonged median survival. Collectively, our data suggest that revisiting a differentiation therapy with forskolin in combination with radiation could lead to clinical benefit.

Indexed as

Brain NeoplasmsCell DifferentiationCell PlasticityColforsinGlioblastomaAnimalsCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticHumansMiceNeoplastic Stem CellsColforsinglioblastomaglioma stem cellsradiotherapy

Identifiers

PMID40009641
PMCPMC11892679

What OpenQuestion holds

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Registered trials

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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.