ArticleCancer biology & therapy2015
Trk inhibitor attenuates the BDNF/TrkB-induced protection of neuroblastoma cells from etoposide in vitro and in vivo.
Article in Cancer biology & therapy, 2015. 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, 25 citations in OpenAlex.
- The neural niche in cancer: mechanistic insights into tumor-neuron-immune crosstalk and therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Advances in Targeting Growth Factor Signalling in Neuroblastoma and Overcoming Drug Resistance.Cells · 2025Review
- Interactions Among Brain-Derived Neurotrophic Factor and Neuroimmune Pathways Are Key Components of the Major Psychiatric Disorders.Molecular neurobiology · 2022Review
- Targeting Oncogenic Transcriptional Networks in Neuroblastoma: From N-Myc to Epigenetic Drugs.International journal of molecular sciences · 2021Review
- Molecular Iodine/Cyclophosphamide Synergism on Chemoresistant Neuroblastoma Models.International journal of molecular sciences · 2021Article
- 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
- The Evolving Diagnostic and Treatment Landscape of NTRK-Fusion-Driven Pediatric Cancers.Paediatric drugs · 2020Review
- The roles played by the MYCN, Trk, and ALK genes in neuroblastoma and neural development.Surgery today · 2019Review
- Antitumor Activities and Cellular Changes Induced by TrkB Inhibition in Medulloblastoma.Frontiers in pharmacology · 2019Article
- Molecularly Targeted Therapy for Neuroblastoma.Children (Basel, Switzerland) · 2018Review
- Cell death-based treatment of neuroblastoma.Cell death & disease · 2018Review
- Neuroblastoma treatment in the post-genomic era.Journal of biomedical science · 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
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
TrkB activation by brain-derived neurotrophic factor (BDNF) contributes to chemo-resistance in neuroblastoma (NB). AZD6918 is a novel potent and selective inhibitor of the Trk tyrosine kinases. In this study we evaluated the effect of AZD6918 on the sensitivity of TrkB-expressing NB cells or tumors to etoposide, a topoisomerase II inhibitor. TrkB-expressing NB cells were treated with AZD6918 and etoposide in the presence or absence of BDNF in vitro and cell survival was determined. NB xenograft tumors were treated with AZD6918 and etoposide, either alone or in combination in vivo, and the anti-tumor growth effect or mice survival advantage was evaluated. Our study showed that AZD6918 induced cell death as a single agent and attenuated BDNF/TrkB-induced protection from etoposide in vitro. Although AZD6918 alone didn't show anti-tumor growth effect or survival advantage in vivo, a combination of AZD6918 and etoposide had a statistically significant stronger anti-tumor growth effect and survival advantage compared to treatment with either agent alone. Our data indicate that as a Trk inhibitor AZD6918 increased the sensitivity of NB to etoposide. These results extend the spectrum of cytotoxic drugs whose efficacy is increased in combination with Trk inhibitors and support the combination of Trk inhibitors and cytotoxic drugs for NB treatment.
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