ArticleMolecular cancer2022
Mutations in ALK signaling pathways conferring resistance to ALK inhibitor treatment lead to collateral vulnerabilities in neuroblastoma cells.
Article in Molecular cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 57 citations in OpenAlex.
- The Role of Precision Medicine in Neuroblastoma: Targeted Therapies and Personalized Approaches-A Narrative Review.Health science reports · 2026Article
- Unveiling the molecular landscape: Long non-coding RNAs in neuroblastoma (Review).Oncology reports · 2026Review
- Pathogenic Neurofibromatosis type 1 gene variants in tumors of non-NF1 patients and role of R1276.FEBS open bio · 2026Article
- Predicting neuroblastoma prognosis using machine learning analysis of metabolism-related gene network perturbation.BMC pediatrics · 2026Article
- Review
- Virtual screening and MD simulation-guided discovery of CDK12-IN-3, a potent ALK inhibitor suppressing neuroblastoma growthFrontiers in chemistry · 2026Article
- Developmentally relevant proteins contribute to chemotherapeutic resistance in neuroblastoma.Frontiers in oncology · 2026Review
- Brain metastases from non-small cell lung cancer: molecular subtypes and emerging CNS-directed precision therapies.Frontiers in oncology · 2026Review
- Advances in Targeting Growth Factor Signalling in Neuroblastoma and Overcoming Drug Resistance.Cells · 2025Review
- Phenotypic plasticity in a novel set of EGFR tyrosine kinase inhibitor-adapted non-small cell lung cancer cell lines.FEBS open bio · 2025Article
- Ganglioside Profiling Uncovers Distinct Patterns in High-Risk Neuroblastoma.International journal of molecular sciences · 2025Article
- Overexpression of miR-29a and miR-29b is involved in imatinib resistance via abrogated NF1 expression and increased ERK1/2 activation in chronic myeloid leukemia cells.Medical oncology (Northwood, London, England) · 2025Article
- Emerging Trends in Neuroblastoma Diagnosis, Therapeutics, and Research.Molecular neurobiology · 2025Review
- Peripheral neuroblastic tumors behaving badly: an update on high-risk morphologic and molecular groupings.Virchows Archiv : an international journal of pathology · 2025Review
- Stratified Medicine Pediatrics: Cell-Free DNA and Serial Tumor Sequencing Identifies Subtype-Specific Cancer Evolution and Epigenetic States.Cancer discovery · 2025Article
- 15 Years Old ALK Gene from Birth to Adolescence; Where to in NBL.Current oncology reports · 2025Review
- Molecular crosstalk between GPCR and receptor tyrosine-protein kinase in neuroblastoma: molecular mechanism and therapeutic implications.Medical oncology (Northwood, London, England) · 2025Review
- Mechanisms and molecular characterization of relapsed/refractory neuroblastomas.Frontiers in oncology · 2025Review
- Quantitative modeling of signaling in aggressive B cell lymphoma unveils conserved core network.PLoS computational biology · 2024Article
- Cell-specific models reveal conformation-specific RAF inhibitor combinations that synergistically inhibit ERK signaling in pancreatic cancer cells.Cell reports · 2024Article
Corrections and comments
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Authors and funding
36 authors at 12 institutions in 3 countries.
Funding
Abstract
backgroundDevelopment of resistance to targeted therapies has tempered initial optimism that precision oncology would improve poor outcomes for cancer patients. Resistance mechanisms, however, can also confer new resistance-specific vulnerabilities, termed collateral sensitivities. Here we investigated anaplastic lymphoma kinase (ALK) inhibitor resistance in neuroblastoma, a childhood cancer frequently affected by activating ALK alterations.
methodsGenome-wide forward genetic CRISPR-Cas9 based screens were performed to identify genes associated with ALK inhibitor resistance in neuroblastoma cell lines. Furthermore, the neuroblastoma cell line NBLW-R was rendered resistant by continuous exposure to ALK inhibitors. Genes identified to be associated with ALK inhibitor resistance were further investigated by generating suitable cell line models. In addition, tumor and liquid biopsy samples of four patients with ALK-mutated neuroblastomas before ALK inhibitor treatment and during tumor progression under treatment were genomically profiled.
resultsBoth genome-wide CRISPR-Cas9-based screens and preclinical spontaneous ALKi resistance models identified NF1 loss and activating NRAS
conclusionsOur results provide a clinically relevant mechanistic model of ALKi resistance in neuroblastoma and highlight new clinically actionable collateral sensitivities in resistant cells.
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