ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
Crizotinib Synergizes with Chemotherapy in Preclinical Models of Neuroblastoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Pooled it
- Frequency and Clinical Significance of Clonal and Subclonal Driver Mutations in High-Risk Neuroblastoma at Diagnosis: A Children's Oncology Group Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Mutated FGFR1 is an oncogenic driver and therapeutic target in high-risk neuroblastoma.The Journal of clinical investigation · 2026Article
- Neuroblastoma in Childhood: Biological Insights, Risk Stratification, and Advances in Multimodal Therapy.Journal of clinical medicine · 2026Review
- D3-GPC2-Directed CAR T Cells Are Safe and Efficacious in Preclinical Models of Neuroblastoma and Small Cell Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Kinome Reprogramming of G2/M Kinases and Repression of MYCN Contribute to Superior Efficacy of Lorlatinib in ALK-Driven Neuroblastoma.Molecular cancer therapeutics · 2025Article
- PanThera: predictive analysis of higher-order combination therapies using deep neural networks.Briefings in bioinformatics · 2025Article
- 15 Years Old ALK Gene from Birth to Adolescence; Where to in NBL.Current oncology reports · 2025Review
- Therapeutic Innovation in Pediatric Neuroblastoma: Age and Stage-Specific Strategies from Prenatal to Early Childhood-A Review Article.Iranian journal of child neurology · 2025Review
- Combined inhibition of histone methyltransferases EZH2 and DOT1L is an effective therapy for neuroblastoma.Cancer medicine · 2024Article
- Antitumor Activity of a Pyrrolobenzodiazepine Antibody-Drug Conjugate Targeting LGR5 in Preclinical Models of Neuroblastoma.Pharmaceutics · 2024Article
- Review
- Narrative review: precision medicine applications in neuroblastoma-current status and future prospects.Translational pediatrics · 2024Review
- Nerve Growth Factor and the Role of Inflammation in Tumor Development.Current issues in molecular biology · 2024Review
- ALK inhibitors increase ALK expression and sensitize neuroblastoma cells to ALK.CAR-T cells.Cancer cell · 2023Article
- Interaction of ALK Inhibitors with Polyspecific Organic Cation Transporters and the Impact of Substrate-Dependent Inhibition on the Prediction of Drug-Drug Interactions.Pharmaceutics · 2023Article
- Metabolic protein kinase signalling in neuroblastoma.Molecular metabolism · 2023Review
- IGF1R Contributes to Cell Proliferation inCancers · 2023Article
- Adaptation of the Th-MYCN Mouse Model of Neuroblastoma for Evaluation of Disseminated Disease.International journal of molecular sciences · 2023Article
- Identification and targeting of protein tyrosine kinase 7 (PTK7) as an immunotherapy candidate for neuroblastoma.Cell reports. Medicine · 2023Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
purposeThe presence of an ALK aberration correlates with inferior survival for patients with high-risk neuroblastoma. The emergence of ALK inhibitors such as crizotinib has provided novel treatment opportunities. However, certain ALK mutations result in de novo crizotinib resistance, and a phase I trial of crizotinib showed a lack of response in patients harboring those ALK mutations. Thus, understanding mechanisms of resistance and defining circumvention strategies for the clinic is critical. EXPERIMENTAL
designThe sensitivity of human neuroblastoma-derived cell lines, cell line-derived, and patient-derived xenograft (PDX) models with varying ALK statuses to crizotinib combined with topotecan and cyclophosphamide (topo/cyclo) was examined. Cultured cells and xenografts were evaluated for effects of these drugs on proliferation, signaling, and cell death, and assessment of synergy.
resultsIn neuroblastoma murine xenografts harboring the most common ALK mutations, including those mutations associated with resistance to crizotinib (but not in those with wild-type ALK), crizotinib combined with topo/cyclo enhanced tumor responses and mouse event-free survival. Crizotinib + topo/cyclo showed synergistic cytotoxicity and higher caspase-dependent apoptosis than crizotinib or topo/cyclo alone in neuroblastoma cell lines with ALK aberrations (mutation or amplification).
conclusionsCombining crizotinib with chemotherapeutic agents commonly used in treating newly diagnosed patients with high-risk neuroblastoma restores sensitivity in preclinical models harboring both sensitive ALK aberrations and de novo-resistant ALK mutations. These data support clinical testing of crizotinib and conventional chemotherapy with the goal of integrating ALK inhibition into multiagent therapy for ALK-aberrant neuroblastoma patients.
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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.