ArticleThe Journal of clinical investigation2020
Orally bioavailable CDK9/2 inhibitor shows mechanism-based therapeutic potential in MYCN-driven neuroblastoma.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 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
50 citing papers in PubMed, 68 citations in OpenAlex.
- Phase I/II Study of the CDK2/9 Inhibitor Fadraciclib in Combination with Chemotherapy in Children with Advanced Malignancies: Arm K of the AcSé-ESMART Trial.Targeted oncology · 2026Trial
- Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Article
- Article
- Targeted therapies in pediatric oncology: A start.Molecular therapy. Oncology · 2026Review
- CDK2 inhibition promotes neuronal differentiation in neuroblastoma.Scientific reports · 2026Article
- Dinaciclib improves treatment response in chemoresistant hepatoblastoma.Scientific reports · 2025Article
- Discovery of a "First-in-Class" Selective Multikinase (CDK4/6/9-AURKA/B) Inhibitor, LCI133, for Neuroblastoma.Journal of medicinal chemistry · 2025Article
- Targeting processive transcription for Myc-driven circuitry in medulloblastoma.Neuro-oncology · 2025Article
- Targeting CDK2 for cancer therapy.Cell reports · 2025Review
- CDK inhibitors promote neuroblastoma cell differentiation and increase sensitivity to retinoic acid-a promising combination strategy for therapeutic intervention.Cell death discovery · 2025Article
- Response of GEM models of neuroblastoma to cabozantinib assessed by multiparametric magnetic resonance imaging.Neoplasia (New York, N.Y.) · 2025Article
- ATRX mutations mediate an immunogenic phenotype and macrophage infiltration in neuroblastoma.Cancer letters · 2025Article
- Wilms tumor primary cultures capture phenotypic heterogeneity and facilitate preclinical screening.Translational oncology · 2025Article
- T cells in the microenvironment of solid pediatric tumors: the case of neuroblastoma.Frontiers in immunology · 2025Review
- Targeting CDK2 to combat drug resistance in cancer therapy.Future oncology (London, England) · 2024Review
- CDK9 inhibitors for the treatment of solid tumors.Biochemical pharmacology · 2024Review
- Review
- The MYCN 5' UTR as a therapeutic target in neuroblastoma.Cell reports · 2024Article
- Targeting Transcriptional Regulation with a CDK9 Inhibitor Suppresses Growth of Endocrine- and Palbociclib-Resistant ER+ Breast Cancers.Cancer research · 2024Article
Corrections and comments
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Authors and funding
43 authors at 11 institutions in 5 countries.
Funding
Abstract
The undruggable nature of oncogenic Myc transcription factors poses a therapeutic challenge in neuroblastoma, a pediatric cancer in which MYCN amplification is strongly associated with unfavorable outcome. Here, we show that CYC065 (fadraciclib), a clinical inhibitor of CDK9 and CDK2, selectively targeted MYCN-amplified neuroblastoma via multiple mechanisms. CDK9 - a component of the transcription elongation complex P-TEFb - bound to the MYCN-amplicon superenhancer, and its inhibition resulted in selective loss of nascent MYCN transcription. MYCN loss led to growth arrest, sensitizing cells for apoptosis following CDK2 inhibition. In MYCN-amplified neuroblastoma, MYCN invaded active enhancers, driving a transcriptionally encoded adrenergic gene expression program that was selectively reversed by CYC065. MYCN overexpression in mesenchymal neuroblastoma was sufficient to induce adrenergic identity and sensitize cells to CYC065. CYC065, used together with temozolomide, a reference therapy for relapsed neuroblastoma, caused long-term suppression of neuroblastoma growth in vivo, highlighting the clinical potential of CDK9/2 inhibition in the treatment of MYCN-amplified neuroblastoma.
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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.