ArticleFrontiers in oncology2015
Downregulation of MYCN through PI3K Inhibition in Mouse Models of Pediatric Neural Cancer.
Article in Frontiers in oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Mycn regulates vascular development through PI3K signaling pathway in zebrafish.Developmental dynamics : an official publication of the American Association of Anatomists · 2026Article
- Latent Association Between Diets and Glioma Risk: A Mendelian Randomization Analysis.Nutrients · 2025Article
- Molecular regulation and therapeutic targeting ofFrontiers in cell and developmental biology · 2025Review
- Revisiting Neuroblastoma: Nrf2, NF-κB and Phox2B as a Promising Network in Neuroblastoma.Current issues in molecular biology · 2024Review
- IGF1R Contributes to Cell Proliferation inCancers · 2023Article
- MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment.Cancers · 2022Review
- The MYCN inhibitor BGA002 restores the retinoic acid response leading to differentiation or apoptosis by the mTOR block in MYCN-amplified neuroblastoma.Journal of experimental & clinical cancer research : CR · 2022Article
- MYCN in Neuroblastoma: "Old Wine into New Wineskins".Diseases (Basel, Switzerland) · 2021Review
- Integrated Genomic Profiling and Drug Screening of Patient-Derived Cultures Identifies Individualized Copy Number-Dependent Susceptibilities Involving PI3K Pathway and 17q Genes in Neuroblastoma.Frontiers in oncology · 2021Article
- Comparing mTOR inhibitor Rapamycin with Torin-2 within the RIST molecular-targeted regimen in neuroblastoma cells.International journal of medical sciences · 2021Article
- Impact of extracellular matrix stiffness on genomic heterogeneity in MYCN-amplified neuroblastoma cell line.Journal of experimental & clinical cancer research : CR · 2020Article
- Targeting MYCN in Molecularly Defined Malignant Brain Tumors.Frontiers in oncology · 2020Review
- TargetingFrontiers in oncology · 2020Review
- Anti-tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL-302 in neuroblastoma.EMBO molecular medicine · 2019Article
- Article
- Improved therapy for medulloblastoma: targeting hedgehog and PI3K-mTOR signaling pathways in combination with chemotherapy.Oncotarget · 2018Article
- p53 Nongenotoxic Activation and mTORC1 Inhibition Lead to Effective Combination for Neuroblastoma Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Association of high microvessel αOncotarget · 2017Article
- The MYCN Protein in Health and Disease.Genes · 2017Review
- Inhibition of mTOR-kinase destabilizes MYCN and is a potential therapy for MYCN-dependent tumors.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The MYCN proto-oncogene is associated with poor outcome across a broad range of pediatric tumors. While amplification of MYCN drives subsets of high-risk neuroblastoma and medulloblastoma, dysregulation of MYCN in medulloblastoma (in the absence of amplification) also contributes to pathogenesis. Since PI3K stabilizes MYCN, we have used inhibitors of PI3K to drive degradation. In this study, we show PI3K inhibitors by themselves induce cell cycle arrest, with modest induction of apoptosis. In screening inhibitors of PI3K against MYCN, we identified PIK-75 and its derivative, PW-12, inhibitors of both PI3K and of protein kinases, to be highly effective in destabilizing MYCN. To determine the effects of PW-12 treatment in vivo, we analyzed a genetically engineered mouse model for MYCN-driven neuroblastoma and a model of MYCN-driven medulloblastoma. PW-12 showed significant activity in both models, inducing vascular collapse and regression of medulloblastoma with prominent apoptosis in both models. These results demonstrate that inhibitors of lipid and protein kinases can drive apoptosis in MYCN-driven cancers and support the importance of MYCN as a therapeutic target.
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Identifiers
What OpenQuestion holds
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.