ArticlePediatric blood & cancer2022
Bromodomain 4 inhibition leads to MYCN downregulation in Wilms tumor.
Article in Pediatric blood & cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- The Effect of AZD5153 on Radiosensitivity in Pancreatic Cancer Cells Through ATM-chk1 Pathway.Drug design, development and therapy · 2026Article
- Pediatric NUT carcinoma: a patient series and literature review.BMC pediatrics · 2025Review
- Wilms' Tumor: A Review of Clinical Characteristics, Treatment Advances, and Research Opportunities.Medicina (Kaunas, Lithuania) · 2025Review
- Wilms tumor primary cultures capture phenotypic heterogeneity and facilitate preclinical screening.Translational oncology · 2025Article
- Review
- Delineating the interplay between oncogenic pathways and immunity in anaplastic Wilms tumors.Nature communications · 2023Article
- Advances in the clinical management of high-risk Wilms tumors.Pediatric blood & cancer · 2023Review
- How engineers and drug developers are working to change childhood cancer's deadly calculus.Nature · 2022Article
- AZD5153, a Bivalent BRD4 Inhibitor, Suppresses Hepatocarcinogenesis by Altering BRD4 Chromosomal Landscape and Modulating the Transcriptome of HCC Cells.Frontiers in cell and developmental biology · 2022Article
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundWilms tumor is the most common childhood kidney cancer. Two distinct histological subtypes of Wilms tumor have been described: tumors lacking anaplasia (the favorable subtype) and tumors displaying anaplastic features (the unfavorable subtype). Children with favorable disease generally have a very good prognosis, whereas those with anaplasia are oftentimes refractory to standard treatments and suffer poor outcomes, leading to an unmet clinical need. MYCN dysregulation has been associated with a number of pediatric cancers including Wilms tumor. PROCEDURES: In this context, we undertook a functional genomics approach to uncover novel therapeutic strategies for those patients with anaplastic Wilms tumor. Genomic analysis and in vitro experimentation demonstrate that cell growth can be reduced by modulating MYCN overexpression via bromodomain 4 (BRD4) inhibition in both anaplastic and nonanaplastic Wilms tumor models.
resultsWe observed a time-dependent reduction of MYCN and MYCC protein levels upon BRD4 inhibition in Wilms tumor cell lines, which led to cell death and proliferation suppression. BRD4 inhibition significantly reduced tumor volumes in Wilms tumor patient-derived xenograft (PDX) mouse models.
conclusionsWe suggest that AZD5153, a novel dual-BRD4 inhibitor, can reduce MYCN levels in both anaplastic and nonanaplastic Wilms tumor cell lines, reduces tumor volume in Wilms tumor PDXs, and should be further explored for its therapeutic potential.
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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.