Observational studyScientific reports2021
MDM4 inhibition: a novel therapeutic strategy to reactivate p53 in hepatoblastoma.
Observational study in Scientific reports, 2021. 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 18 papers.
What it found
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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.
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.
Who cites it
18 citing papers in PubMed, 40 citations in OpenAlex.
- Dependence on Mdm2 for Mdm4 inhibition of p53 activity.Cancer letters · 2025Article
- Small glycomimetic antagonists of the cytomegalovirus glycoprotein UL141 prevent binding to TRAIL death receptor.The Journal of biological chemistry · 2025Article
- Upregulation of YPEL3 expression and induction of human breast cancer cell death by microRNAs.Toxicological research · 2024Article
- Summary of biological research on hepatoblastoma: a scoping review.Frontiers in pediatrics · 2024Article
- Characterizing intergenic transcription at RNA polymerase II binding sites in normal and cancer tissues.Cell genomics · 2023Article
- Identification of the Stapled α-Helical Peptide ATSP-7041 as a Substrate and Strong Inhibitor of OATP1B1 In Vitro.Biomolecules · 2023Article
- Article
- Article
- Article
- Brentuximab vedotin as a bridge to combination chemotherapy in gray zone lymphoma with severe liver impairment: a case report.Frontiers in oncology · 2023Article
- Hepatoblastomas with carcinoma features represent a biological spectrum of aggressive neoplasms in children and young adults.Journal of hepatology · 2022Article
- Current Approaches in Hepatoblastoma-New Biological Insights to Inform Therapy.Current oncology reports · 2022Review
- Review
- Unravelling Mechanisms of Doxorubicin-Induced Toxicity in 3D Human Intestinal Organoids.International journal of molecular sciences · 2022Article
- Utilization of macrocyclic peptides to target protein-protein interactions in cancer.Frontiers in oncology · 2022Review
- The Curious Case of the HepG2 Cell Line: 40 Years of Expertise.International journal of molecular sciences · 2021Review
- Integrative Analysis of DNA Methylation and Gene Expression Profiling Data Reveals Candidate Methylation-Regulated Genes in Hepatoblastoma.International journal of general medicine · 2021Article
- The Mutual Inhibition of FoxO1 and SREBP-1c Regulated the Progression of Hepatoblastoma by Regulating Fatty Acid Metabolism.Mediators of inflammation · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
Hepatoblastoma (HB) is the most common pediatric liver malignancy. High-risk patients have poor survival, and current chemotherapies are associated with significant toxicities. Targeted therapies are needed to improve outcomes and patient quality of life. Most HB cases are TP53 wild-type; therefore, we hypothesized that targeting the p53 regulator Murine double minute 4 (MDM4) to reactivate p53 signaling may show efficacy. MDM4 expression was elevated in HB patient samples, and increased expression was strongly correlated with decreased expression of p53 target genes. Treatment with NSC207895 (XI-006), which inhibits MDM4 expression, or ATSP-7041, a stapled peptide dual inhibitor of MDM2 and MDM4, showed significant cytotoxic and antiproliferative effects in HB cells. Similar phenotypes were seen with short hairpin RNA (shRNA)-mediated inhibition of MDM4. Both NSC207895 and ATSP-7041 caused significant upregulation of p53 targets in HB cells. Knocking-down TP53 with shRNA or overexpressing MDM4 led to resistance to NSC207895-mediated cytotoxicity, suggesting that this phenotype is dependent on the MDM4-p53 axis. MDM4 inhibition also showed efficacy in a murine model of HB with significantly decreased tumor weight and increased apoptosis observed in the treatment group. This study demonstrates that inhibition of MDM4 is efficacious in HB by upregulating p53 tumor suppressor signaling.
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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.