ArticleOncotarget2014
Activated Alk triggers prolonged neurogenesis and Ret upregulation providing a therapeutic target in ALK-mutated neuroblastoma.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Systematic review of the receptor tyrosine kinase superfamily in neuroblastoma pathophysiology.Cancer metastasis reviews · 2022Pooled it
- Single-nucleus RNA sequencing reveals GABAergic vulnerability and reactive gliosis driven by loss of TDP-43.iScience · 2025Article
- Trajectory analysis reveals an uncommitted neuroblastic state in MYCN-driven neuroblastoma development.Neuro-oncology · 2025Article
- Peripheral neuroblastic tumors behaving badly: an update on high-risk morphologic and molecular groupings.Virchows Archiv : an international journal of pathology · 2025Review
- Defining neuroblastoma: From origin to precision medicine.Neuro-oncology · 2024Review
- Article
- Small Molecule Tyrosine Kinase Inhibitors (TKIs) for Glioblastoma Treatment.International journal of molecular sciences · 2024Review
- The intricate interplay between cancer stem cells and cell-of-origin of cancer: implications for therapeutic strategies.Frontiers in oncology · 2024Review
- Germline Variants in Cancer Predisposition Genes in Pediatric Patients with Central Nervous System Tumors.International journal of molecular sciences · 2023Article
- Multifaceted Roles of ALK Family Receptors and Augmentor Ligands in Health and Disease: A Comprehensive Review.Biomolecules · 2023Review
- Targeting the RET tyrosine kinase in neuroblastoma: A review and application of a novel selective drug design strategy.Biochemical pharmacology · 2023Review
- Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.Pharmaceutics · 2023Review
- In toto imaging of early enteric nervous system development reveals that gut colonization is tied to proliferation downstream of Ret.Development (Cambridge, England) · 2022Article
- Patient-associated mutations in Drosophila Alk perturb neuronal differentiation and promote survival.Disease models & mechanisms · 2022Article
- Article
- Review
- Defining Pathological Activities of ALK in Neuroblastoma, a Neural Crest-Derived Cancer.International journal of molecular sciences · 2021Review
- MYCN in Neuroblastoma: "Old Wine into New Wineskins".Diseases (Basel, Switzerland) · 2021Review
- NTRK1/TrkA Signaling in Neuroblastoma Cells Induces Nuclear Reorganization and Intra-Nuclear Aggregation of Lamin A/C.Cancers · 2021Article
- Neuroblastoma Formation Requires Unconventional CD4 T Cells and Arginase-1-Dependent Myeloid Cells.Cancer research · 2021Article
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activating mutations of the ALK (Anaplastic lymphoma Kinase) gene have been identified in sporadic and familial cases of neuroblastoma, a cancer of early childhood arising from the sympathetic nervous system (SNS). To decipher ALK function in neuroblastoma predisposition and oncogenesis, we have characterized knock-in (KI) mice bearing the two most frequent mutations observed in neuroblastoma patients. A dramatic enlargement of sympathetic ganglia is observed in AlkF1178L mice from embryonic to adult stages associated with an increased proliferation of sympathetic neuroblasts from E14.5 to birth. In a MYCN transgenic context, the F1178L mutation displays a higher oncogenic potential than the R1279Q mutation as evident from a shorter latency of tumor onset. We show that tumors expressing the R1279Q mutation are sensitive to ALK inhibition upon crizotinib treatment. Furthermore, our data provide evidence that activated ALK triggers RET upregulation in mouse sympathetic ganglia at birth as well as in murine and human neuroblastoma. Using vandetanib, we show that RET inhibition strongly impairs tumor growth in vivo in both MYCN/KI AlkR1279Q and MYCN/KI AlkF1178L mice. Altogether, our findings demonstrate the critical role of activated ALK in SNS development and pathogenesis and identify RET as a therapeutic target in ALK mutated neuroblastoma.
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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.