ArticleOncogene2010
Amplification of EGFR T790M causes resistance to an irreversible EGFR inhibitor.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
What it found
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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
122 citing papers in PubMed, 227 citations in OpenAlex.
- Phase 2 study of intermittent pulse dacomitinib in patients with advanced non-small cell lung cancers.Lung cancer (Amsterdam, Netherlands) · 2017Trial
- Trial
- Opportunities and challenges in the development of evolving EGFR inhibitors to overcome EGFR TKIs resistance.Acta pharmacologica Sinica · 2026Review
- EGFR inhibitor-resistant lung cancers exhibit collateral sensitivity to a covalent, cysteine-independent KEAP1 oligomerizing molecular bridge.Nature communications · 2026Article
- Peritoneal Metastasis in Advanced Lung Adenocarcinoma Harboring EGFR Exon 19 Deletion/T790M with STRN::ALK Fusion and EGFR Kinase Domain Duplication: Two Case Reports and a Narrative Literature Summary.Cancer management and research · 2026Article
- Elevated plasma HSP90α as a prognostic marker in EGFR-mutant non-small cell lung cancer.Oncology letters · 2025Article
- EGFR mutations in non-small cell lung cancer: Classification, characteristics and resistance to third-generation EGFR-tyrosine kinase inhibitors (Review).Oncology letters · 2025Review
- Article
- mRNA vaccines transform personalized lung cancer treatment.Frontiers in immunology · 2025Review
- Allosteric ligand-driven smart nanoconjugates for mutation-selective EGFR targeting: A precision approach to overcoming tyrosine kinase inhibitor resistance.BioImpacts : BI · 2025Review
- FGFR3 alterations in bladder cancer: Sensitivity and resistance to targeted therapies.Cancer communications (London, England) · 2024Review
- The evolutionary theory of cancer: challenges and potential solutions.Nature reviews. Cancer · 2024Review
- Activating Point Mutations in the MET Kinase Domain Represent a Unique Molecular Subset of Lung Cancer and Other Malignancies Targetable with MET Inhibitors.Cancer discovery · 2024Article
- Alectinib continuation beyond progression inTranslational lung cancer research · 2024Article
- Kras oncogene ablation prevents resistance in advanced lung adenocarcinomas.The Journal of clinical investigation · 2023Article
- Emerging roles of PHLPP phosphatases in lung cancer.Frontiers in oncology · 2023Review
- Convergent evolution and multi-wave clonal invasion in H3 K27-altered diffuse midline gliomas treated with a PDGFR inhibitor.Acta neuropathologica communications · 2022Article
- Plasticity of Extrachromosomal and Intrachromosomal BRAF Amplifications in Overcoming Targeted Therapy Dosage Challenges.Cancer discovery · 2022Article
- Non-small-cell lung cancer: how to manageDrugs in context · 2022Review
- Extrachromosomal Circular DNA: A New Target in Cancer.Frontiers in oncology · 2022Review
62 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
13 authors at 5 institutions in 1 country.
Funding
Abstract
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib are effective therapies against mutant non-small cell lung cancers (NSCLCs). Treatment is limited by the development of resistance in part explained by the gain of a secondary EGFR mutation, T790M, at the gatekeeper residue. Irreversible EGFR inhibitors, including PF00299804, are effective in vitro and in vivo against EGFR mutant tumors that contain EGFR T790M and are currently under clinical development. In this study, we generate models of resistance to PF00299804, using cell lines with EGFR T790M and show that the PF00299804-resistant models develop focal amplification of EGFR that preferentially involves the T790M-containing allele. These PF00299804-resistant cell lines remain dependent on EGFR for growth as downregulation of EGFR by shRNA compromises their viability. We show that resistance to PF00299804 arises, at least in part, through selection of a pre-existing EGFR T790M-amplified clone both in vitro and using a xenograft model in vivo. Our findings show that EGFR T790M is a common resistance mechanism to both reversible, and when amplified, the irreversible EGFR kinase inhibitors further emphasizing the need to develop more potent therapies against EGFR T790M. These findings can be used to guide studies of patient tumor specimens from ongoing clinical trials of irreversible EGFR kinase inhibitors.
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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.