ArticleDisease models & mechanisms2016
The ALK inhibitor PF-06463922 is effective as a single agent in neuroblastoma driven by expression of ALK and MYCN.
Article in Disease models & mechanisms, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 83 citations in OpenAlex.
- Review
- A structure-based virtual screening approach to identify novel anaplastic lymphoma kinase inhibitors.Journal of molecular modeling · 2026Article
- Therapeutic benefit of the dual ALK/FAK inhibitor ESK440 in ALK-driven neuroblastoma.Neoplasia (New York, N.Y.) · 2025Article
- Emerging clinical and research approaches in targeted therapies for high-risk neuroblastoma.Frontiers in oncology · 2025Review
- Recent Advancement in Drug Designing as Small Molecules in Targeted Cancer Therapy: Challenges and Future Directions.Current cancer drug targets · 2025Review
- Unveiling Tumorigenesis Mechanisms and Drug Therapy in Neuroblastoma by Mass Spectrometry Based Proteomics.Children (Basel, Switzerland) · 2024Review
- Long-Lasting Response to Lorlatinib in Patients with ALK-Driven Relapsed or Refractory Neuroblastoma Monitored with Circulating Tumor DNA Analysis.Cancer research communications · 2024Article
- Sequential Analysis of cfDNA Reveals Clonal Evolution in Patients with Neuroblastoma Receiving ALK-Targeted Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- ALK signaling primes the DNA damage response sensitizing ALK-driven neuroblastoma to therapeutic ATR inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Negr1-Derived Peptides Trigger ALK Degradation and Halt Neuroblastoma Progression In Vitro and In Vivo.Pharmaceutics · 2023Article
- Metabolic protein kinase signalling in neuroblastoma.Molecular metabolism · 2023Review
- IGF1R Contributes to Cell Proliferation inCancers · 2023Article
- ALK Amplification and Rearrangements Are Recurrent Targetable Events in Congenital and Adult Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Circulating tumor DNA reveals mechanisms of lorlatinib resistance in patients with relapsed/refractory ALK-driven neuroblastoma.Nature communications · 2023Article
- Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.Pharmaceutics · 2023Review
- ATR inhibition enables complete tumour regression in ALK-driven NB mouse models.Nature communications · 2021Article
- Synthetic Heterocyclic Derivatives as Kinase Inhibitors Tested for the Treatment of Neuroblastoma.Molecules (Basel, Switzerland) · 2021Review
- Translational Strategies for Repotrectinib in Neuroblastoma.Molecular cancer therapeutics · 2021Article
- Frequency and Prognostic Impact ofJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 3 countries.
Funding
Abstract
The first-in-class inhibitor of ALK, c-MET and ROS1, crizotinib (Xalkori), has shown remarkable clinical efficacy in treatment of ALK-positive non-small cell lung cancer. However, in neuroblastoma, activating mutations in the ALK kinase domain are typically refractory to crizotinib treatment, highlighting the need for more potent inhibitors. The next-generation ALK inhibitor PF-06463922 is predicted to exhibit increased affinity for ALK mutants prevalent in neuroblastoma. We examined PF-06463922 activity in ALK-driven neuroblastoma models in vitro and in vivo In vitro kinase assays and cell-based experiments examining ALK mutations of increasing potency show that PF-06463922 is an effective inhibitor of ALK with greater activity towards ALK neuroblastoma mutants. In contrast to crizotinib, single agent administration of PF-06463922 caused dramatic tumor inhibition in both subcutaneous and orthotopic xenografts as well as a mouse model of high-risk neuroblastoma driven by Th-ALK(F1174L)/MYCN Taken together, our results suggest PF-06463922 is a potent inhibitor of crizotinib-resistant ALK mutations, and highlights an important new treatment option for neuroblastoma patients.
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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.