ArticleNature2008
Activating mutations in ALK provide a therapeutic target in neuroblastoma.
Article in Nature, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 450 papers.
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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
450 citing papers in PubMed, 888 citations in OpenAlex.
- Circulating Beta3-Adrenoreceptor as Novel Independent Biomarker for Risk Assessment in Neuroblastoma Patients.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
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- Golgi Retention and Oncogenic Signaling of KIT Tyrosine Kinase in Gastrointestinal Stromal Tumor.Sub-cellular biochemistry · 2026Review
- Article
- Chromosomal instability degrades developmental phenotypes essential for anti-GD2 immunotherapy outcomes in high-risk neuroblastoma.Cell reports. Medicine · 2025Article
- Integration of ALK gene mutations and targeted therapies in pediatric high-risk neuroblastoma: advancements in precision oncology.Annals of medicine and surgery (2012) · 2025Review
- Kinome Reprogramming of G2/M Kinases and Repression of MYCN Contribute to Superior Efficacy of Lorlatinib in ALK-Driven Neuroblastoma.Molecular cancer therapeutics · 2025Article
- Pulmonary Toxicity Associated With Concurrent Lorlatinib and Anti-GD2 Monoclonal Antibody Therapy in Patients With Neuroblastoma.Pediatric blood & cancer · 2025Article
- Ganglioside Profiling Uncovers Distinct Patterns in High-Risk Neuroblastoma.International journal of molecular sciences · 2025Article
- A humanized anaplastic lymphoma kinase (ALK)-directed antibody-drug conjugate with pyrrolobenzodiazepine payload demonstrates efficacy in ALK-expressing cancers.Nature communications · 2025Article
- Colchicine Binding Site Tubulin Inhibitors Impair Vincristine-Resistant Neuroblastoma Cell Function.Molecules (Basel, Switzerland) · 2025Article
- ALK in cancer: from function to therapeutic targeting.Nature reviews. Cancer · 2025Review
- Identifying Genes Associated with the Anticancer Activity of a Fluorinated Chalcone in Triple-Negative Breast Cancer Cells Using Bioinformatics Tools.International journal of molecular sciences · 2025Article
- 15 Years Old ALK Gene from Birth to Adolescence; Where to in NBL.Current oncology reports · 2025Review
- Anaplastic Lymphoma Kinase Inhibition Therapy for Hereditary Neuroblastoma.JCO precision oncology · 2025Article
- Therapeutic benefit of the dual ALK/FAK inhibitor ESK440 in ALK-driven neuroblastoma.Neoplasia (New York, N.Y.) · 2025Article
- Case Report: 3 cases of abdominal lesions with lower limb lymphedema-rare mutations in complex lymphatic anomalies.Frontiers in oncology · 2025Article
- The NSUN5 gene rs1880948 A>G polymorphism and neuroblastoma risk in Chinese children.Frontiers in oncology · 2025Article
- Antibody conjugates in neuroblastoma: a step forward in precision medicine.Frontiers in oncology · 2025Review
- Discovery of novel anaplastic lymphoma kinase (ALK) and histone deacetylase (HDAC) dual inhibitors exhibiting antiproliferative activity against non-small cell lung cancer.Journal of enzyme inhibition and medicinal chemistry · 2024Article
390 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 9 institutions in 2 countries.
Funding
Abstract
Neuroblastoma, an embryonal tumour of the peripheral sympathetic nervous system, accounts for approximately 15% of all deaths due to childhood cancer. High-risk neuroblastomas are rapidly progressive; even with intensive myeloablative chemotherapy, relapse is common and almost uniformly fatal. Here we report the detection of previously unknown mutations in the ALK gene, which encodes a receptor tyrosine kinase, in 8% of primary neuroblastomas. Five non-synonymous sequence variations were identified in the kinase domain of ALK, of which three were somatic and two were germ line. The most frequent mutation, F1174L, was also identified in three different neuroblastoma cell lines. ALK complementary DNAs encoding the F1174L and R1275Q variants, but not the wild-type ALK cDNA, transformed interleukin-3-dependent murine haematopoietic Ba/F3 cells to cytokine-independent growth. Ba/F3 cells expressing these mutations were sensitive to the small-molecule inhibitor of ALK, TAE684 (ref. 4). Furthermore, two human neuroblastoma cell lines harbouring the F1174L mutation were also sensitive to the inhibitor. Cytotoxicity was associated with increased amounts of apoptosis as measured by TdT-mediated dUTP nick end labelling (TUNEL). Short hairpin RNA (shRNA)-mediated knockdown of ALK expression in neuroblastoma cell lines with the F1174L mutation also resulted in apoptosis and impaired cell proliferation. Thus, activating alleles of the ALK receptor tyrosine kinase are present in primary neuroblastoma tumours and in established neuroblastoma cell lines, and confer sensitivity to ALK inhibition with small molecules, providing a molecular rationale for targeted therapy of this disease.
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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.