ArticleScientific reports2016
Novel ALK inhibitor AZD3463 inhibits neuroblastoma growth by overcoming crizotinib resistance and inducing apoptosis.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Stalling the Enemy: Targeting Nsp13 for Next-Generation SARS-CoV-2 Antivirals.International journal of molecular sciences · 2026Article
- Virtual screening and MD simulation-guided discovery of CDK12-IN-3, a potent ALK inhibitor suppressing neuroblastoma growthFrontiers in chemistry · 2026Article
- Advances in Targeting Growth Factor Signalling in Neuroblastoma and Overcoming Drug Resistance.Cells · 2025Review
- Review
- Review
- Therapeutic Targeting of the Anaplastic Lymphoma Kinase (ALK) in Neuroblastoma-A Comprehensive Update.Pharmaceutics · 2021Review
- ALK inhibition activates LC3B-independent, protective autophagy in EML4-ALK positive lung cancer cells.Scientific reports · 2021Article
- Combination of AZD3463 and DZNep Prevents Bone Metastasis of Breast Cancer by Suppressing Akt Signaling.Frontiers in pharmacology · 2021Article
- Article
- Polyethylene glycol derivative 9bw suppresses growth of neuroblastoma cells by inhibiting oxidative phosphorylation.Cancer science · 2020Article
- Role of Indole Scaffolds as Pharmacophores in the Development of Anti-Lung Cancer Agents.Molecules (Basel, Switzerland) · 2020Review
- AZD3463, an IGF-1R inhibitor, suppresses breast cancer metastasis to bone via modulation of the PI3K-Akt pathway.Annals of translational medicine · 2020Article
- The ALK inhibitor AZD3463 effectively inhibits growth of sorafenib-resistant acute myeloid leukemia.Blood cancer journal · 2019Article
- Cell-Based Methods for Determination of Efficacy for Candidate Therapeutics in the Clinical Management of Cancer.Diseases (Basel, Switzerland) · 2018Review
- The Akt/mTOR pathway in cancer stem/progenitor cells is a potential therapeutic target for glioblastoma and neuroblastoma.Oncotarget · 2018Article
- Article
- Genetic susceptibility to neuroblastoma: current knowledge and future directions.Cell and tissue research · 2018Review
- Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus.Nature communications · 2018Article
- Cell death-based treatment of neuroblastoma.Cell death & disease · 2018Review
- Small molecule inhibitor regorafenib inhibits RET signaling in neuroblastoma cells and effectively suppresses tumor growthOncotarget · 2017Article
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Authors and funding
21 authors at 6 institutions in 2 countries.
Funding
Abstract
ALK receptor tyrosine kinase has been shown to be a therapeutic target in neuroblastoma. Germline ALK activating mutations are responsible for the majority of hereditary neuroblastoma and somatic ALK activating mutations are also frequently observed in sporadic cases of advanced NB. Crizotinib, a first-line therapy in the treatment of advanced non-small cell lung cancer (NSCLC) harboring ALK rearrangements, demonstrates striking efficacy against ALK-rearranged NB. However, crizotinib fails to effectively inhibit the activity of ALK when activating mutations are present within its kinase domain, as with the F1174L mutation. Here we show that a new ALK inhibitor AZD3463 effectively suppressed the proliferation of NB cell lines with wild type ALK (WT) as well as ALK activating mutations (F1174L and D1091N) by blocking the ALK-mediated PI3K/AKT/mTOR pathway and ultimately induced apoptosis and autophagy. In addition, AZD3463 enhanced the cytotoxic effects of doxorubicin on NB cells. AZD3463 also exhibited significant therapeutic efficacy on the growth of the NB tumors with WT and F1174L activating mutation ALK in orthotopic xenograft mouse models. These results indicate that AZD3463 is a promising therapeutic agent in the treatment of NB.
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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.