ArticleCancer chemotherapy and pharmacology2012
AZ64 inhibits TrkB and enhances the efficacy of chemotherapy and local radiation in neuroblastoma xenografts.
Article in Cancer chemotherapy and pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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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.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Chronic military stress and glandular epithelial tumor biology: an integrative neuroendocrine-inflammatory framework with insights from microgravity gene discovery.Frontiers in oncology · 2026Article
- Sprouty in Tumors of the Nervous System.International journal of molecular sciences · 2025Review
- Knockdown of NCOR2 Inhibits Cell Proliferation via BDNF/TrkB/ERK in NF1-Derived MPNSTs.Cancers · 2022Article
- Molecular targeting therapies for neuroblastoma: Progress and challenges.Medicinal research reviews · 2021Review
- An overview of neuroblastoma cell lineage phenotypes andExperimental biology and medicine (Maywood, N.J.) · 2020Review
- RET receptor expression and interaction with TRK receptors in neuroblastomas.Oncology reports · 2020Article
- Spontaneous regression of neuroblastoma.Cell and tissue research · 2018Review
- Entrectinib and other ALK/TRK inhibitors for the treatment of neuroblastoma.Drug design, development and therapy · 2018Review
- Targeting Epigenetic Pathways in the Treatment of Pediatric Diffuse (High Grade) Gliomas.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017Review
- PI3K and MAPK pathways mediate the BDNF/TrkB-increased metastasis in neuroblastoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Trk inhibition reduces cell proliferation and potentiates the effects of chemotherapeutic agents in Ewing sarcoma.Oncotarget · 2016Article
- Entrectinib is a potent inhibitor of Trk-driven neuroblastomas in a xenograft mouse model.Cancer letters · 2016Article
- Pediatric cerebellar astrocytoma: a review.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2015Review
- TrkB inhibition by GNF-4256 slows growth and enhances chemotherapeutic efficacy in neuroblastoma xenografts.Cancer chemotherapy and pharmacology · 2015Article
- Trk inhibitor attenuates the BDNF/TrkB-induced protection of neuroblastoma cells from etoposide in vitro and in vivo.Cancer biology & therapy · 2015Article
- Management of high-grade gliomas in the pediatric patient: Past, present, and future.Neuro-oncology practice · 2014Article
- Molecular profiling of childhood cancer: Biomarkers and novel therapies.BBA clinical · 2014Review
- Therapeutic targets for neuroblastomas.Expert opinion on therapeutic targets · 2014Review
- Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma.Nature genetics · 2013Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Neuroblastoma is a common pediatric tumor characterized by clinical heterogeneity. Because it is derived from sympathetic neuroblasts, the NTRK family of neurotrophin receptors plays an integral role in neuroblastoma cell survival, growth, and differentiation. Indeed, high expression of NTRK1 is associated with favorable clinical features and outcome, whereas expression of NTRK2 and its ligand, brain-derived neurotrophic factor (BDNF), are associated with unfavorable features and outcome. AZ64 (Astra Zeneca) is a potent and selective inhibitor of the NTRK tyrosine kinases that blocks phosphorylation at nanomolar concentrations. To determine the preclinical activity of AZ64, we performed intervention trials in a xenograft model with NTRK2-overexpressing neuroblastomas. AZ64 alone significantly inhibited tumor growth compared to vehicle-treated animals (p = 0.0006 for tumor size). Furthermore, the combination of AZ64 with conventional chemotherapeutic agents, irinotecan and temozolomide (irino-temo), showed significantly enhanced anti-tumor efficacy compared to irino-temo alone [(p < 0.0001 for tumor size, p < 0.0005 for event-free survival (EFS)]. We also assessed the combination of AZ64 and local radiation therapy (RT) on a neuroblastoma hindlimb xenograft model, and the efficacy of local RT was significantly increased when animals were treated simultaneously with AZ64 (p < 0.0001 for tumor size, p = 0.0006 for EFS). We conclude that AZ64 can inhibit growth of NTRK-expressing neuroblastomas both in vitro and in vivo. More importantly, it can significantly enhance the efficacy of conventional chemotherapy as well as local RT, presumably by inhibition of the NTRK2/BDNF autocrine survival pathway.
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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.