ArticleMolecular cancer2021
Intercellular transfer of exosomal wild type EGFR triggers osimertinib resistance in non-small cell lung cancer.
Article in Molecular cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 139 citations in OpenAlex.
- CPT1A-mediated IDO1 succinylation shapes EGFRvIII-driven resistance to tumor electric field therapy in glioblastoma.Nature communications · 2026Article
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- Lung tumour secretome and extracellular vesicles: mechanisms, biomarkers, and therapeutic opportunities.Cancer metastasis reviews · 2026Review
- Identification of TRPM4 related genes in LUAD by RNA seq and spatial transcriptomics.Discover oncology · 2026Article
- VDAC1 protein derived from extracellular vesicles promotes paclitaxel resistance in gastric cancer through autophagy and mitophagy.Cancer biology & medicine · 2026Article
- Research on exosomes in cancer multidrug resistance and clinical translation.Extracellular vesicles and circulating nucleic acids · 2026Review
- RAB3A-mediated BAG6 translocation promotes non-small cell lung cancer tumorigenesis and progression.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Exosomes promote pre-metastatic niche formation in lung cancer.Cancer cell international · 2025Review
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- PPARγ controls ESCRT-dependent fibroblast-like synoviocyte exosome biogenesis and alleviates chondrocyte osteoarthritis mediated by exosomal ANXA1.Journal of orthopaedic translation · 2025Article
- Application of liquid biopsy in differentiating lung cancer from benign pulmonary nodules (Review).International journal of molecular medicine · 2025Review
- Evaluating the Effectiveness of Tyrosine Kinase Inhibitors on EGFR Mutations In Vitro.International journal of molecular sciences · 2025Article
- Exofection by exosomes: A transient functional cargo transfer.Extracellular vesicle · 2025Article
- Exosome-Mediated Chemoresistance in Cancers: Mechanisms, Therapeutic Implications, and Future Directions.Biomolecules · 2025Review
- Strategies Beyond 3rd EGFR-TKI Acquired Resistance: Opportunities and Challenges.Cancer medicine · 2025Review
- Emerging roles of exosomal circRNAs in non-small cell lung cancer.Journal of translational medicine · 2025Review
- Harnessing Exosomes: A Brief Overview of Nature's Nanocarriers and a Glimpse into Their Implications in Pituitary Neuroendocrine Tumors (PitNETs).Current issues in molecular biology · 2025Review
- Revolutionizing lung cancer treatment: harnessing exosomes as early diagnostic biomarkers, therapeutics and nano-delivery platforms.Journal of nanobiotechnology · 2025Review
- Extracellular vesicles in cancer´s communication: messages we can read and how to answer.Molecular cancer · 2025Review
27 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEpidermal growth factor receptor (EGFR)-mutated lung cancer constitutes a major subgroup of non-small cell lung cancer (NSCLC) and osimertinib is administrated as first-line treatment. However, most patients with osimertinib treatment eventually relapse within one year. The underlying mechanisms of osimertinib resistance remain largely unexplored.
methodsExosomes isolation was performed by differential centrifugation. Co-culture assays were conducted to explore the alteration of drug sensitivity by cell viability and apoptosis assays. Immunofluorescence and flow cytometry were performed to visualize the formation or absorption of exosomes. Exosomes secretion was measured by Nanoparticle Tracking Analysis or ELISA. The xenograft tumor model in mice was established to evaluate the effect of exosomes on osimertinib sensitivity in vivo.
resultsIntercellular transfer of exosomal wild type EGFR protein confers osimertinib resistance to EGFR-mutated sensitive cancer cells in vitro and in vivo. Co-culture of EGFR-mutated sensitive cells and EGFR-nonmutated resistant cells promoted osimertinib resistance phenotype in EGFR-mutated cancer cells, while depletion of exosomes from conditioned medium or blockade of exosomal EGFR by neutralizing antibody alleviated this phenotype. Mechanistically, osimertinib promoted the release of exosomes by upregulated a Rab GTPase (RAB17). Knockdown of RAB17 resulted in the decrease of exosomes secretion. Moreover, exosomes could be internalized by EGFR-mutated cancer cells via Clathrin-dependent endocytosis and then the encapsulated exosomal wild type EGFR protein activated downstream PI3K/AKT and MAPK signaling pathways and triggered osimertinib resistance.
conclusionsIntercellular transfer of exosomal wild type EGFR promotes osimertinib resistance in NSCLC, which may represent a novel resistant mechanism of osimertinib and provide a proof of concept for targeting exosomes to prevent and reverse the osimertinib resistance.
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