ArticleMolecular cancer2018
A new ALK isoform transported by extracellular vesicles confers drug resistance to melanoma cells.
Article in Molecular cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Distant Metastasis in Colorectal Cancer Patients-Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review.International journal of molecular sciences · 2020Pooled it
- Fusion gene heterogeneity and kinase enrichment in high-grade serous carcinomas.Neoplasia (New York, N.Y.) · 2026Article
- Out-of-frame CBX3::ALK fusion drives ALK activation and therapy response.Cell reports. Medicine · 2026Article
- TRMU Confers Resistance of Melanoma Cells to Vemurafenib through Modulating Mitochondrial Activities.Journal of proteome research · 2025Article
- Extracellular vesicles promote migration despite BRAF inhibitor treatment in malignant melanoma cells.Cell communication and signaling : CCS · 2024Article
- Protein Biomarker Discovery Studies on Urinary sEV Fractions Separated with UF-SEC for the First Diagnosis and Detection of Recurrence in Bladder Cancer Patients.Biomolecules · 2023Article
- TERT Expression Induces Resistance to BRAF and MEK Inhibitors in BRAF-Mutated Melanoma In Vitro.Cancers · 2023Article
- Adopted neoplastic cells and the consequences of their existence.Oncotarget · 2023Article
- Review
- Extracellular Vesicles-Based Cell-Cell Communication in Melanoma: New Perspectives in Diagnostics and Therapy.International journal of molecular sciences · 2023Review
- Extracellular Vesicles in Cancer Drug Resistance: Roles, Mechanisms, and Implications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Review
- Characterization of Vemurafenib-Resistant Melanoma Cell Lines Reveals Novel Hallmarks of Targeted Therapy Resistance.International journal of molecular sciences · 2022Article
- Clinical features, molecular pathology, and immune microenvironmental characteristics of acral melanoma.Journal of translational medicine · 2022Review
- Article
- Review
- Review
- Gene Identification and Potential Drug Therapy for Drug-Resistant Melanoma with Bioinformatics and Deep Learning Technology.Disease markers · 2022Article
- Review
- Differential Splicing of Skipped Exons Predicts Drug Response in Cancer Cell Lines.Genomics, proteomics & bioinformatics · 2021Article
- Review
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDrug resistance remains an unsolved clinical issue in oncology. Despite promising initial responses obtained with BRAF and MEK kinase inhibitors, resistance to treatment develops within months in virtually all melanoma patients.
methodsMicroarray analyses were performed in BRAF inhibitor-sensitive and resistant cell lines to identify changes in the transcriptome that might play a role in resistance. siRNA approaches and kinase inhibitors were used to assess the involvement of the identified Anaplastic Lymphoma Kinase (ALK) in drug resistance. The capability of extracellular vesicles (EVs) to transfer drug resistant properties was investigated in co-culture assays.
resultsHere, we report a new mechanism of acquired drug resistance involving the activation of a novel truncated form of ALK. Knock down or inhibition of ALK re-sensitised resistant cells to BRAF inhibition and induced apoptosis. Interestingly, truncated ALK was also secreted into EVs and we show that EVs were the vehicle for transferring drug resistance.
conclusionsTo our knowledge, this is the first report demonstrating the functional involvement of EVs in melanoma drug resistance by transporting a truncated but functional form of ALK, able to activate the MAPK signalling pathway in target cells. Combined inhibition of ALK and BRAF dramatically reduced tumour growth in vivo. These findings make ALK a promising clinical target in melanoma patients.
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