ArticleCell reports2021
Transcriptional control of DNA repair networks by CDK7 regulates sensitivity to radiation in MYC-driven medulloblastoma.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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.
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Who cites it
28 citing papers in PubMed, 43 citations in OpenAlex.
- Sensitizing tumor response to topoisomerase I antibody-drug conjugate by selective CDK7 inhibition.Science advances · 2026Article
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- Paediatric therapeutic development workshop on osteosarcoma.British journal of cancer · 2026Review
- Rapid Optimization Enabled by Single-Molecule Tracking: Discovery of a Potent RUVBL1/2 Inhibitor to Evaluate the Targeting of MYC-Driven Cancers.Journal of medicinal chemistry · 2026Article
- Transcriptional regulation of protein synthesis by mediator kinase represents a therapeutic vulnerability in MYC-driven medulloblastoma.Nature communications · 2025Article
- High-resolution proteomic analysis of medulloblastoma clinical samples identifies therapy-resistant subgroups and MYC immunohistochemistry as a powerful outcome predictor.Neuro-oncology · 2025Article
- Targeting processive transcription for Myc-driven circuitry in medulloblastoma.Neuro-oncology · 2025Article
- Multi-omics analysis reveals RNA polymerase II degradation as a novel mechanism of PF-3758309's anti-tumor activity.Cell death discovery · 2025Article
- Development of an Anti-CD99 Antibody Enables Targeting of Diffuse Midline Glioma.Cancer research · 2025Article
- Targeting CDK7 Enhances the Antitumor Efficacy of Enzalutamide in Androgen Receptor-Positive Triple-Negative Breast Cancer by Inhibiting c-MYC-mediated Tumorigenesis.Molecular cancer therapeutics · 2025Article
- Physiological and pathological roles of the transcriptional kinases CDK12 and CDK13 in the central nervous system.Cell death and differentiation · 2025Review
- Inhibition of cyclin-dependent kinase 7 mitigates doxorubicin cardiotoxicity and enhances anticancer efficacy.Cardiovascular research · 2024Article
- Multifunctional Fluoropolymer-Engineered Magnetic Nanoparticles to Facilitate Blood-Brain Barrier Penetration and Effective Gene Silencing in Medulloblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Triptolide and its prodrug Minnelide target high-risk MYC-amplified medulloblastoma in preclinical models.The Journal of clinical investigation · 2024Article
- Co-overexpression of BRD4 and CDK7 promotes cell proliferation and predicts poor prognosis in HCC.Heliyon · 2024Article
- Transcriptional pausing induced by ionizing radiation enables the acquisition of radioresistance in nasopharyngeal carcinoma.Journal of molecular cell biology · 2024Article
- Pharmacological inhibition of MYC to mitigate chemoresistance in preclinical models of squamous cell carcinoma.Theranostics · 2024Article
- EYA2 tyrosine phosphatase inhibition reduces MYC and prevents medulloblastoma progression.Neuro-oncology · 2023Article
- MYC up-regulation confers vulnerability to dual inhibition of CDK12 and CDK13 in high-risk Group 3 medulloblastoma.Journal of experimental & clinical cancer research : CR · 2023Article
- Dissecting super-enhancer driven transcriptional dependencies reveals novel therapeutic strategies and targets for group 3 subtype medulloblastoma.Journal of experimental & clinical cancer research : CR · 2022Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
MYC-driven medulloblastoma is a major therapeutic challenge due to frequent metastasis and a poor 5-year survival rate. MYC gene amplification results in transcriptional dysregulation, proliferation, and survival of malignant cells. To identify therapeutic targets in MYC-amplified medulloblastoma, we employ a CRISPR-Cas9 essentiality screen targeting 1,140 genes. We identify CDK7 as a mediator of medulloblastoma tumorigenesis. Using chemical inhibitors and genetic depletion, we observe cessation of tumor growth in xenograft mouse models and increases in apoptosis. The results are attributed to repression of a core set of MYC-driven transcriptional programs mediating DNA repair. CDK7 inhibition alters RNA polymerase II (RNA Pol II) and MYC association at DNA repair genes. Blocking CDK7 activity sensitizes cells to ionizing radiation leading to accrual of DNA damage, extending survival and tumor latency in xenograft mouse models. Our studies establish the selective inhibition of MYC-driven medulloblastoma by CDK7 inhibition combined with radiation as a viable therapeutic strategy.
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Registered trials
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.