Evidence map›Paper›PMID 40372972›Full record

ArticleNeuro-oncology2025

Targeting processive transcription for Myc-driven circuitry in medulloblastoma.

Lays Martin Sobral, Faye M Walker, Krishna Madhavan, Elizabeth Janko, Sahiti Donthula, Etienne Danis, Pradeep Bompada, Ilango Balakrishnan, Dong Wang, Angela Pierce and 8 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 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Preclinical evaluation of ixazomib for high-risk pediatric brain tumors.bioRxiv : the preprint server for biology · 2026
    Article
  2. Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  3. Review
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Lays Martin SobralMorgan Adams Foundation Pediatric Brain Tumor Research Program, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.
Faye M WalkerMorgan Adams Foundation Pediatric Brain Tumor Research Program, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.
Krishna MadhavanMorgan Adams Foundation Pediatric Brain Tumor Research Program, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.
Elizabeth JankoMorgan Adams Foundation Pediatric Brain Tumor Research Program, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.
Sahiti DonthulaMorgan Adams Foundation Pediatric Brain Tumor Research Program, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.
Etienne DanisBiostatistics and Bioinformatics, University of Colorado School of Medicine, Aurora, Colorado, USA.ORCID 0000-0002-5651-8111
Pradeep BompadaMorgan Adams Foundation Pediatric Brain Tumor Research Program, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.
Ilango BalakrishnanMorgan Adams Foundation Pediatric Brain Tumor Research Program, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.
Dong WangMorgan Adams Foundation Pediatric Brain Tumor Research Program, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.ORCID 0000-0002-7652-1692
Angela PierceMorgan Adams Foundation Pediatric Brain Tumor Research Program, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.
Mary M HaagColorado Genetics Laboratory, Department of Pathology, University of Colorado School of Medicine, Aurora, Colorado, USA.
Billie J CarstensColorado Genetics Laboratory, Department of Pathology, University of Colorado School of Medicine, Aurora, Colorado, USA.
Natalie J SerkovaDepartment of Radiology, University of Colorado School of Medicine, Aurora, Colorado, USA.
Nicholas K ForemanDepartment of Neurosurgery, University of Colorado School of Medicine, Aurora, Colorado, USA.
Sujatha VenkataramanMorgan Adams Foundation Pediatric Brain Tumor Research Program, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.ORCID 0000-0002-1512-284X
Bethany VeoMorgan Adams Foundation Pediatric Brain Tumor Research Program, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.
Rajeev VibhakarDepartment of Neurosurgery, University of Colorado School of Medicine, Aurora, Colorado, USA.
Nathan A DahlCenter for Cancer and Blood Disorders, Children's Hospital Colorado, Aurora, Colorado, USA.ORCID 0000-0003-2555-1741

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Targeting Wee1 in Myc driven MedulloblasomaR01NS091219 · NINDS · UNIVERSITY OF COLORADO DENVER · PI Rajeev Vibhakar · 2015 to 2026
$3.3M
Bruker 9.4T/ 20cm BioSpec MR Scanner for Colorado Animal Imaging Shared ResourcesS10OD023485 · OD · UNIVERSITY OF COLORADO DENVER · PI SERKOVA, NATALIE J. · 2017 to 2017
$2.0M
CDK9-mediated processive transcription in H3K27M+ diffuse intrinsic pontine gliomaK08NS121592 · NINDS · UNIVERSITY OF COLORADO DENVER · PI DAHL, NATHAN A · 2021 to 2025
$949k
NCI NIH HHS P30 CA046934NIH HHS S10 OD023485NINDS NIH HHS K08 NS121592NINDS NIH HHS K08NS121592NINDS NIH HHS R01 NS091219NINDS NIH HHS R01NS091219ODCDC CDC HHS S10 OD023485University of Colorado Cancer Center/Molecular, Cellular, and Developmental Biology MUJP.2021.003
6 · The paper itself

Abstract

backgroundMedulloblastoma is the most common malignant brain tumor of childhood. The highest-risk tumors are driven by recurrent Myc amplifications (Myc-MB) and experience poorer outcomes despite intensive multimodal therapy. The Myc transcription factor defines core regulatory circuitry for these tumors and acts to broadly amplify downstream pro-survival transcriptional programs. Therapeutic targeting of Myc directly has proven elusive, but inhibiting transcriptional cofactors may present an indirect means of drugging the oncogenic transcriptional circuitry sustaining Myc-MB.

methodsIndependent CRISPR-Cas9 screens were pooled to identify conserved dependencies in Myc-MB. We performed chromatin conformation capture (Hi-C) from primary patient Myc-MB samples to map enhancer-promoter interactions. We then treated in vitro and xenograft models with CDK9/7 inhibitors to evaluate the effect on Myc-driven programs and tumor growth.

resultsEight CRISPR-Cas9 screens performed across 3 independent labs identify CDK9 as a conserved dependency in Myc-MB. Myc-MB cells are susceptible to CDK9 inhibition, which is synergistic with concurrent inhibition of CDK7. Inhibition of transcriptional CDKs disrupts enhancer-promoter activity in Myc-MB and downregulates Myc-driven transcriptional programs, exerting a potent antitumor effect.

conclusionsOur findings identify CDK9 inhibition as a translationally promising strategy for the treatment of Myc-MB.

Indexed as

Cerebellar NeoplasmsGene Expression Regulation, NeoplasticMedulloblastomaProto-Oncogene Proteins c-mycTranscription, GeneticAnimalsCell ProliferationCRISPR-Cas SystemsCyclin-Dependent Kinase 9HumansMiceTumor Cells, CulturedXenograft Model Antitumor AssaysCyclin-Dependent Kinase 9MYC protein, humanProto-Oncogene Proteins c-mycCDK7CDK9medulloblastomaMyc

Identifiers

PMID40372972
PMCPMC12833536

What OpenQuestion holds

Textmetadata
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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.