ArticleFrontiers in oncology2012
Molecular mechanisms of MYCN-dependent apoptosis and the MDM2-p53 pathway: an Achille's heel to be exploited for the therapy of MYCN-amplified neuroblastoma.
Article in Frontiers in oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 24 citations in OpenAlex.
- Effect ofJCO precision oncology · 2026Article
- SGSS05-NS3, a covalent SETD8 inhibitor that activates p53 pathway in neuroblastoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Targeting the MYCN-MDM2 pathways for cancer therapy: Are they druggable?Genes & diseases · 2025Review
- Delineating the Molecular Events Underlying Development of Prostate Cancer Variants with Neuroendocrine/Small Cell Carcinoma Characteristics.International journal of molecular sciences · 2021Review
- A combination of PARP and CHK1 inhibitors efficiently antagonizes MYCN-driven tumors.Oncogene · 2021Article
- Targeting the p53-MDM2 pathway for neuroblastoma therapy: Rays of hope.Cancer letters · 2021Review
- Article
- HMGA Genes and Proteins in Development and Evolution.International journal of molecular sciences · 2020Review
- TargetingFrontiers in oncology · 2020Review
- Comprehensive evaluation of context dependence of the prognostic impact of MYCN amplification in neuroblastoma: A report from the International Neuroblastoma Risk Group (INRG) project.Pediatric blood & cancer · 2019Article
- Microenvironment in neuroblastoma: isolation and characterization of tumor-derived mesenchymal stromal cells.BMC cancer · 2018Article
- MRE11 inhibition highlights a replication stress-dependent vulnerability of MYCN-driven tumors.Cell death & disease · 2018Article
- Article
- PARP inhibitors enhance replication stress and cause mitotic catastrophe in MYCN-dependent neuroblastoma.Oncogene · 2017Article
- High-SETD8 inactivates p53 in neuroblastoma.Oncoscience · 2017Article
- Epigenetic siRNA and Chemical Screens Identify SETD8 Inhibition as a Therapeutic Strategy for p53 Activation in High-Risk Neuroblastoma.Cancer cell · 2017Article
- miR-34a inhibits the apoptosis of MDSCs by suppressing the expression of N-myc.Immunology and cell biology · 2016Article
- Galectin-3 is a marker of favorable prognosis and a biologically relevant molecule in neuroblastic tumors.Cell death & disease · 2014Article
- Editorial: Targeting MYCN in Pediatric Cancers.Frontiers in oncology · 2014Article
- Neuroblastoma: developmental biology, cancer genomics and immunotherapy.Nature reviews. Cancer · 2013Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The p53 oncosuppressor is very seldom mutated in neuroblastoma, but several mechanisms cooperate to its functional inactivation in this tumor. Increased MDM2 levels, due to genetic amplification or constitutive inhibition of p14( ARF), significantly contribute to this event highlighting p53 reactivation as an attractive perspective for neuroblastoma treatment. In addition to its role in tumorigenesis, MYCN sensitizes untransformed and cancer cells to apoptosis. This is associated to a fine modulation of the MDM2-p53 pathway. Indeed MYCN induces p53 and MDM2 transcription, and, by evoking a DNA damage response (DDR), it stabilizes p53 and its proapoptotic kinase Homeodomain Interacting Protein Kinase 2 (HIPK2). Through the regulation of the HIPK2-p53 inhibitor High Mobility Group protein A1 (HMGA1) and the homeobox proteins BMI-1 and TWIST-1, MYCN establishes a delicate balance between pro- and antiapoptotic molecules that might be easily perturbed by a variety of insults, leading to cell death. MDM2-p53 antagonists, such as Nutlin-3, are strikingly prone to inducing death in MYCN-amplified neuroblastoma, by further pushing on HIPK2 accumulation. Here we discuss implications and caveats of exploiting this pathway and its connections to MYCN-induced DDR for a tailored therapy of MYCN-amplified neuroblastoma.
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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.