ArticleCell death discovery2018
The p53 activator overcomes resistance to ALK inhibitors by regulating p53-target selectivity in ALK-driven neuroblastomas.
Article in Cell death discovery, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Dissecting cross-lineage tumourigenesis under p53 inactivation through single-cell multi-omics and spatial transcriptomics.Clinical and translational medicine · 2025Article
- Investigating the Cell Origin and Liver Metastasis Factors of Colorectal Cancer by Single-Cell Transcriptome Analysis.OncoTargets and therapy · 2024Article
- Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Telomerase-targeting compounds Imetelstat and 6-thio-dG act synergistically with chemotherapy in high-risk neuroblastoma models.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Ceritinib (LDK378) prevents bone lossFrontiers in endocrinology · 2022Article
- Review
- Genomic and evolutionary classification of lung cancer in never smokers.Nature genetics · 2021Article
- ALK Inhibitors-Induced M Phase Delay Contributes to the Suppression of Cell Proliferation.Cancers · 2020Article
- The role of MDM2-p53 axis dysfunction in the hepatocellular carcinoma transformation.Cell death discovery · 2020Review
- Do Mutations Turn p53 into an Oncogene?International journal of molecular sciences · 2019Review
- Discovery, characterization and potential roles of a novel NF-YAx splice variant in human neuroblastoma.Journal of experimental & clinical cancer research : CR · 2019Article
- Prediction of PD-L1 Expression in Neuroblastoma via Computational Modeling.Brain sciences · 2019Article
- Review
- Alectinib, an Anaplastic Lymphoma Kinase Inhibitor, Abolishes ALK Activity and Growth in ALK-Positive Neuroblastoma Cells.Frontiers in oncology · 2019Article
- Challenging tumor resistance with less toxic, more effective drug combinations: an example from neuroblastoma.Cell death & disease · 2018Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anaplastic lymphoma kinase (ALK) is an oncogenic receptor tyrosine kinase that is activated by gene amplification and mutation in neuroblastomas. ALK inhibitors can delay the progression of ALK-driven cancers, but are of limited use owing to ALK inhibitor resistance. Here, we show that resistance to ALK inhibitor in ALK-driven neuroblastomas can be attenuated by combination treatment with a p53 activator. Either ALK inhibition or p53 activator treatment induced cell cycle arrest, whereas combination treatment induced apoptosis, and prevented tumour relapse both in vitro and in vivo. This shift toward apoptosis, and away from cell-cycle arrest, in the presence of an ALK inhibitor and a p53 activator, is mediated by inhibition of the ALK-AKT-FOXO3a axis leading to a specific upregulation of SOX4. SOX4 cooperates with p53 to upregulate the pro-apoptotic protein PUMA. These data therefore suggest a novel combination therapy strategy for treating ALK-driven neuroblastomas.
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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.