ArticleCancer research2013
Acquired resistance to EGFR inhibitors is associated with a manifestation of stem cell-like properties in cancer cells.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
159 citing papers in PubMed, 271 citations in OpenAlex.
- Phase II trial of a non-platinum triplet for patients with advanced non-small cell lung carcinoma (NSCLC) overexpressing ERCC1 messenger RNA.Thoracic cancer · 2019Trial
- Phase I/II study of gefitinib (Iressa(®)) and vorinostat (IVORI) in previously treated patients with advanced non-small cell lung cancer.Cancer chemotherapy and pharmacology · 2015Trial
- DNA base lesion-containing G-quadruplex mediates transcriptome reprogramming in EGFR-TKI resistance of non-small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Beyond immune surveillance: IFN-γ and PD-L1 as shapers of tumor plasticity in Non-Small Cell Lung Cancer (NSCLC).Frontiers in immunology · 2026Review
- Combined treatment of TKIs with Cilengitide overcomes afatinib-resistance in EGFR-mutated NSCLC cells.Molecular biology reports · 2025Article
- Inhibition of BRD4 sensitizes NSCLC cells to osimertinib by suppressing APT1 and promoting MST1 palmitoylation.Cell death discovery · 2025Article
- Bioinformatics analysis of the expression of TRIM31 mRNA and protein in pan-cancer tissues and their prognostic relevance.Scientific reports · 2025Article
- The Role of Mesenchymal Stem Cells in Drug Resistance in Lung Neoplasms.Journal of cancer prevention · 2025Review
- Relationship between systemic immune-inflammation index and all-cause mortality in stages IIIB-IV epidermal growth factor receptor-mutated lung adenocarcinoma.Frontiers in endocrinology · 2025Article
- The Intricate Web of MicroRNAs in Modulating EGFR-TKI Resistance in Non-Small Cell Lung Cancer: A Comprehensive Review.Cancer management and research · 2025Review
- The Impact of Bevacizumab and miR200c on EMT and EGFR-TKI Resistance in EGFR-Mutant Lung Cancer Organoids.Genes · 2024Article
- The Impact of Inadequate Exposure to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors on the Development of Resistance in Non-Small-Cell Lung Cancer Cells.International journal of molecular sciences · 2024Article
- Three-Dimensional Tumor Models to Study Cancer Stemness-Mediated Drug Resistance.Cellular and molecular bioengineering · 2024Review
- Low-Dose Sorafenib Promotes Cancer Stem Cell Expansion and Accelerated Tumor Progression in Soft Tissue Sarcomas.International journal of molecular sciences · 2024Article
- miR-204 suppresses cancer stemness and enhances osimertinib sensitivity in non-small cell lung cancer by targeting CD44.Molecular therapy. Nucleic acids · 2024Article
- Tanreqing injection inhibits stemness and enhances sensitivity of non-small cell lung cancer models to gefitinib through ROS/STAT3 signaling pathway.Journal of Cancer · 2024Article
- Exploring olfactory receptor family 7 subfamily C member 1 as a novel oral cancer stem cell target for immunotherapy.Cancer science · 2023Article
- 6-Shogaol Overcomes Gefitinib Resistance via ER Stress in Ovarian Cancer Cells.International journal of molecular sciences · 2023Article
- MonitoringFrontiers in oncology · 2023Review
- Effects of cilengitide derivatives on TGF-β1-induced epithelial-to-mesenchymal transition and invasion in gefitinib-resistant non-small cell lung cancer cells.Frontiers in pharmacology · 2023Article
99 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Acquired resistance to EGF receptor (EGFR) tyrosine kinase inhibitor (TKI) is a critical problem in the treatment of lung cancer. Although several mechanisms have been shown to be responsible for acquired resistance, all mechanisms have not been uncovered. In this study, we investigated the molecular and cellular profiles of the acquired resistant cells to EGFR-TKI in EGFR-mutant lung cancers. Four EGFR-mutant cell lines were exposed to gefitinib by stepwise escalation and high-concentration exposure methods, and resistant sublines to gefitinib were established. The molecular profiles and cellular phenotypes of these resistant sublines were characterized. Although previously reported, alterations including secondary EGFR T790M mutation, MET amplification, and appearance of epithelial-to-mesenchymal transition (EMT) features were observed, these 2 drug-exposure methods revealed different resistance mechanisms. The resistant cells with EMT features exhibited downregulation of miRNA-200c by DNA methylation. Furthermore, the HCC827-derived subline characterized by the high-concentration exposure method exhibited not only EMT features but also stem cell-like properties, including aldehyde dehydrogenase isoform 1 (ALDH1A1) overexpression, increase of side-population, and self-renewal capability. Resistant sublines with stem cell-like properties were resistant to conventional chemotherapeutic agents but equally sensitive to histone deacetylase and proteasome inhibitors, compared with their parental cells. ALDH1A1 was upregulated in clinical samples with acquired resistance to gefitinib. In conclusion, our study indicates that the manner of EGFR-TKI exposure influences the mechanism of acquired resistance and the appearance of stem cell-like property with EGFR-TKI treatment.
Indexed as
Identifiers
What OpenQuestion holds
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.