ArticleTranslational oncology2020
Small-Molecule Dual PLK1 and BRD4 Inhibitors are Active Against Preclinical Models of Pediatric Solid Tumors.
Article in Translational oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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.
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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
15 citing papers in PubMed, 28 citations in OpenAlex.
- PAX3: A Driver of Normal Development and Disease.Biomolecules · 2026Review
- Targeting the MYCN-MDM2 pathways for cancer therapy: Are they druggable?Genes & diseases · 2025Review
- Elimusertib has Antitumor Activity in Preclinical Patient-Derived Pediatric Solid Tumor Models.Molecular cancer therapeutics · 2024Article
- Targeting CBX3 with a Dual BET/PLK1 Inhibitor Enhances the Antitumor Efficacy of CDK4/6 Inhibitors in Prostate Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Class I HDAC inhibitor entinostat synergizes with PLK1 inhibitors in MYC-amplified medulloblastoma cells.Journal of neuro-oncology · 2023Article
- When Just One Phosphate Is One Too Many: The Multifaceted Interplay between Myc and Kinases.International journal of molecular sciences · 2023Review
- Combined inhibition of BET bromodomain and mTORC1/2 provides therapeutic advantage for rhabdomyosarcoma by switching cell death mechanism.Molecular carcinogenesis · 2022Article
- Therapeutic targeting of ATR in alveolar rhabdomyosarcoma.Nature communications · 2022Article
- Article
- Drug target inference by mining transcriptional data using a novel graph convolutional network framework.Protein & cell · 2022Article
- Dual-target inhibitors of bromodomain and extra-terminal proteins in cancer: A review from medicinal chemistry perspectives.Medicinal research reviews · 2022Review
- Patient-derived models: Advanced tools for precision medicine in neuroblastoma.Frontiers in oncology · 2022Review
- Synthetic Heterocyclic Derivatives as Kinase Inhibitors Tested for the Treatment of Neuroblastoma.Molecules (Basel, Switzerland) · 2021Review
- Epigenetic-Based Therapy-A Prospective Chance for Medulloblastoma Patients' Recovery.International journal of molecular sciences · 2021Review
- Molecular Mechanisms ofFrontiers in oncology · 2020Review
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Simultaneous inhibition of multiple molecular targets is an established strategy to improve the continuance of clinical response to therapy. Here, we screened 49 molecules with dual nanomolar inhibitory activity against BRD4 and PLK1, best classified as dual kinase-bromodomain inhibitors, in pediatric tumor cell lines for their antitumor activity. We identified two candidate dual kinase-bromodomain inhibitors with strong and tumor-specific activity against neuroblastoma, medulloblastoma, and rhabdomyosarcoma tumor cells. Dual PLK1 and BRD4 inhibitor treatment suppressed proliferation and induced apoptosis in pediatric tumor cell lines at low nanomolar concentrations. This was associated with reduced MYCN-driven gene expression as assessed by RNA sequencing. Treatment of patient-derived xenografts with dual inhibitor UMB103 led to significant tumor regression. We demonstrate that concurrent inhibition of two central regulators of MYC protein family of protooncogenes, BRD4, and PLK1, with single small molecules has strong and specific antitumor effects in preclinical pediatric cancer models.
Identifiers
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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 Socratic graph.