ArticleCancer research2006
Inhibition of phosphatidylinositol 3-kinase destabilizes Mycn protein and blocks malignant progression in neuroblastoma.
Article in Cancer research, 2006. 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 123 papers.
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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
123 citing papers in PubMed, 198 citations in OpenAlex.
- Novel pharmacodynamic biomarkers for MYCN protein and PI3K/AKT/mTOR pathway signaling in children with neuroblastoma.Molecular oncology · 2016Trial
- Paediatric therapeutic development workshop on medulloblastoma.British journal of cancer · 2026Review
- Clinical management and therapeutic development for the rare disease rhabdomyosarcoma.Journal of Cancer · 2026Review
- A Phase 1 Trial of Fimepinostat in Children and Adolescents With Relapsed and Refractory Solid and CNS Tumors.Cancer medicine · 2025Article
- Fimepinostat is a dual inhibitor of tumor and angiogenesis in glioblastoma and synergizes with temozolomide through suppressing MYC.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- Myc family proteins: Molecular drivers of tumorigenesis and resistance in neuroendocrine tumors.Biochimica et biophysica acta. Reviews on cancer · 2025Review
- 15 Years Old ALK Gene from Birth to Adolescence; Where to in NBL.Current oncology reports · 2025Review
- Targeting the MYCN-MDM2 pathways for cancer therapy: Are they druggable?Genes & diseases · 2025Review
- Emerging clinical and research approaches in targeted therapies for high-risk neuroblastoma.Frontiers in oncology · 2025Review
- Unveiling Tumorigenesis Mechanisms and Drug Therapy in Neuroblastoma by Mass Spectrometry Based Proteomics.Children (Basel, Switzerland) · 2024Review
- Paediatric strategy forum for medicinal product development of PI3-K, mTOR, AKT and GSK3β inhibitors in children and adolescents with cancer.European journal of cancer (Oxford, England : 1990) · 2024Review
- Preclinical Therapeutic Efficacy of RAF/MEK/ERK and IGF1R/AKT/mTOR Inhibition in Neuroblastoma.Cancers · 2024Article
- The dual HDAC and PI3K inhibitor, CUDC‑907, inhibits tumor growth and stem‑like properties by suppressing PTX3 in neuroblastoma.International journal of oncology · 2024Article
- Investigating the molecular mechanisms of Fuzheng Yiliu Shenji prescription in SH-SY5Y neuroblastoma cells.Frontiers in oncology · 2024Article
- Kinases Controlling Stability of the Oncogenic MYCN Protein.ACS medicinal chemistry letters · 2023Article
- Metabolic protein kinase signalling in neuroblastoma.Molecular metabolism · 2023Review
- IGF1R Contributes to Cell Proliferation inCancers · 2023Article
- AKT inhibitor Hu7691 induces differentiation of neuroblastoma cells.Acta pharmaceutica Sinica. B · 2023Article
- Targeting ARHGEF12 promotes neuroblastoma differentiation, MYCN degradation, and reduces tumorigenicity.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- A Review of the Regulatory Mechanisms of N-Myc on Cell Cycle.Molecules (Basel, Switzerland) · 2023Review
63 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Amplification of MYCN occurs commonly in neuroblastoma. We report that phosphatidylinositol 3-kinase (PI3K) inhibition in murine neuroblastoma (driven by a tyrosine hydroxylase-MYCN transgene) led to decreased tumor mass and decreased levels of Mycn protein without affecting levels of MYCN mRNA. Consistent with these observations, PI3K inhibition in MYCN-amplified human neuroblastoma cell lines resulted in decreased levels of Mycn protein without affecting levels of MYCN mRNA and caused decreased proliferation and increased apoptosis. To clarify the importance of Mycn as a target of broad-spectrum PI3K inhibitors, we transduced wild-type N-myc and N-myc mutants lacking glycogen synthase kinase 3beta phosphorylation sites into human neuroblastoma cells with no endogenous expression of myc. In contrast to wild-type N-myc, the phosphorylation-defective mutant proteins were stabilized and were resistant to the antiproliferative effects of PI3K inhibition. Our results show the importance of Mycn as a therapeutic target in established tumors in vivo, offer a mechanistic rationale to test PI3K inhibitors in MYCN-amplified neuroblastoma, and represent a therapeutic approach applicable to a broad range of cancers in which transcription factors are stabilized through a PI3K-dependent mechanism.
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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.