ArticleTargeted oncology2015
Afatinib resistance in non-small cell lung cancer involves the PI3K/AKT and MAPK/ERK signalling pathways and epithelial-to-mesenchymal transition.
Article in Targeted oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Role of signaling pathways in lung cancer development and advances in targeted therapies (Review).Oncology letters · 2025Review
- Therapeutic advances of targeting receptor tyrosine kinases in cancer.Signal transduction and targeted therapy · 2024Review
- The multifaceted role of extracellular vesicles in prostate cancer-a review.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Long non-coding RNAs in non-small cell lung cancer: implications for EGFR-TKI resistance.Frontiers in genetics · 2023Review
- Fbxo45-mediated NP-STEPMolecular oncology · 2022Article
- Overexpression of Teashirt Homolog 2 suppresses cell proliferation and predicts the favorable survival of Lung Adenocarcinoma.International journal of medical sciences · 2021Observational
- MAP2K1 is a potential therapeutic target in erlotinib resistant head and neck squamous cell carcinoma.Scientific reports · 2019Article
- Blocking TBK1 alleviated radiation-induced pulmonary fibrosis and epithelial-mesenchymal transition through Akt-Erk inactivation.Experimental & molecular medicine · 2019Article
- Biological Evaluation and Molecular Dynamics Simulation of Chalcone Derivatives as Epidermal Growth Factor-Tyrosine Kinase Inhibitors.Molecules (Basel, Switzerland) · 2019Article
- Direct activation of PP2A for the treatment of tyrosine kinase inhibitor-resistant lung adenocarcinoma.JCI insight · 2019Article
- Efficacy of afatinib in aOncoTargets and therapy · 2019Article
- ENKUR acts as a tumor suppressor in lung adenocarcinoma cells through PI3K/Akt and MAPK/ERK signaling pathways.Journal of Cancer · 2019Article
- Anti-tumor activity of Shikonin against afatinib resistant non-small cell lung cancer via negative regulation of PI3K/Akt signaling pathway.Bioscience reports · 2018Article
- Anesthetic effects of isoflurane and the molecular mechanism underlying isoflurane‑inhibited aggressiveness of hepatic carcinoma.Molecular medicine reports · 2018Article
- RNF25 promotes gefitinib resistance in EGFR-mutant NSCLC cells by inducing NF-κB-mediated ERK reactivation.Cell death & disease · 2018Article
- CXCL5 regulation of proliferation and migration in human non-small cell lung cancer cells.Journal of physiology and biochemistry · 2018Article
- Article
- Review
- Additive effects of cherlerythrine chloride combination with erlotinib in human non-small cell lung cancer cells.PloS one · 2017Article
- Superior efficacy of co-treatment with the dual PI3K/mTOR inhibitor BEZ235 and histone deacetylase inhibitor Trichostatin A against NSCLC.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The epidermal growth factor receptor (EGFR) signalling is one of the most deregulated pathways in non-small cell lung cancer (NSCLC). Recently, the development of novel irreversible tyrosine kinase inhibitors (TKI), such as afatinib, has significantly improved the survival of advanced NSCLC patients harbouring activated EGFR mutations. However, treatment with TKI is not always curative due to the development of resistance. In the present study, we investigated the sensitivity to afatinib in two NSCLC EGFR mutated cell lines (NCI-H1650 and NCI-H1975) by expression profile analysis of 92 genes involved in the EGF pathway. Thereafter, the established afatinib resistant clones were evaluated at different biological levels: genomic, by array comparative genomic hybridisation (aCGH) and deep sequencing; transcriptomic, by quantitative polymerase chain reaction (qPCR) and proteomic, by Western blot and immunofluorescence. The baseline gene expression of the two cell lines revealed that NCI-H1650, the less afatinib-responsive cell, showed activation of two main EGFR downstream pathways such as PI3K/AKT and PLCγ/PKC axes. Analysis of the afatinib-resistant cells showed PI3K/AKT and MAPK/ERK pathways activation together with a biological switch from an epithelial-to-mesenchymal phenotype might confer afatinib-resistant properties to this cell line. Our data suggest that the activation of EGFR-dependent downstream pathways might be involved in the occurrence of resistance to afatinib assuming that the EGFR mutational status should not be exclusively considered when selecting TKI treatments. In particular, the epithelial-to-mesenchymal transition might provide a new basis for understanding afatinib resistance.
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