ArticleScience translational medicine2011
Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors.
Article in Science translational medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 1,855 papers, 7 of them syntheses that pooled it.
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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.
Circulating Tumor DNA (ctDNA) as a Prognostic Tool in Patients With Advanced Lung Adenocarcinoma
Retrospective Study of Cases of Small Cell Lung Cancer (SCLC) That Appeared During Treatment of Another Lung Carcinoma With or Without Oncogenic Activation (TransCPC)
An Observational Study to Assess the Molecular Epidemiology of Epidermal Growth Factor Receptor (EGFR) Mutations in Patients With Advanced EGFR Mutation-positive Non-small Cell Lung Cancer Treated With Afatinib in Real-world Clinical Set-tings in Greece
The CCANED-CIPHER Study: Early Cancer Detection and Treatment Response Monitoring Using AI-Based Platelet and Immune Cell Transcriptomic Profiling
Who cites it
1,855 citing papers in PubMed, 7 syntheses or guidelines pooled it.
- Histological transformation in lung cancer: a single-arm meta-analysis and systematic review.BMC cancer · 2026Pooled it
- Insights into pet-based radiogenomics in oncology: an updated systematic review.European journal of nuclear medicine and molecular imaging · 2025Pooled it
- [Histological Transformation from Non-small Cell Lung Cancer to Small Cell Lung Cancer Induced by Immune Checkpoint Inhibitor Therapy: A Case Report and Literature Review].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Pooled it
- Immune Checkpoint Inhibitors in Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor-Resistant Chemotherapy-Naïve Advanced Non-Small Cell Lung Cancer: A Meta-Analysis Based on Eight Randomized Trials.JCO precision oncology · 2025Pooled it
- Adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for the treatment of people with resected stage I to III non-small-cell lung cancer and EGFR mutation.The Cochrane database of systematic reviews · 2025Pooled it
- Pooled it
- Patients outcomes in lung adenocarcinoma transforming to small-cell lung cancer after tyrosine kinase inhibitor therapy.World journal of surgical oncology · 2025Pooled it
- The pathway alteration load is a pan-cancer determinant of outcome of targeted therapies: results from the Drug Rediscovery Protocol (DRUP).ESMO open · 2025Trial
- Gefitinib (an EGFR tyrosine kinase inhibitor) plus anlotinib (an multikinase inhibitor) for untreated, EGFR-mutated, advanced non-small cell lung cancer (FL-ALTER): a multicenter phase III trial.Signal transduction and targeted therapy · 2024Trial
- Polycomb scaffolding subunit EED supports the SCLC neuroendocrine identity and EGFR-mutant LUAD-to-SCLC transformation.The Journal of clinical investigation · 2026Article
- Reframing cancer therapy through tumor plasticity.Nature cancer · 2026Review
- Lineage identity governs oncogene dependence in mouse NSCLC models of KRAS inhibitor resistance.Nature genetics · 2026Article
- Serial ctDNA Analysis for Monitoring Molecular Response and Acquired Resistance in Metastatic NSCLC and HR+/HER2-Negative Breast Cancer: A Real-World Study.Cancer medicine · 2026Article
- Loss of lineage fidelity underpins drug resistance in Kras-mutant lung cancer.Nature genetics · 2026Article
- Dissecting residual disease in spheroids reveals pan-cancer persistence signatures and a therapeutic window for oncolytic viruses.Molecular therapy. Oncology · 2026Article
- PAX5 modulates vascularization and contributes to neuroendocrine lineage transition during carcinoma progression.The Journal of clinical investigation · 2026Article
- Longitudinal spatial multi-omics delineates tumor microenvironment remodeling across sequential EGFR-TKIs in EGFR-mutant NSCLC.Journal of translational medicine · 2026Article
- Article
- Deconvolution of evolutionary architecture unmasks a high-risk, subclonal-rich subtype in treatment-naive small cell lung cancer.Journal of thoracic disease · 2026Article
- Adaptive epithelial-mesenchymal bi-directional transition: A key invasive plasticity for tumor metastasis.iScience · 2026Review
1,795 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors.
Funding
Abstract
Lung cancers harboring mutations in the epidermal growth factor receptor (EGFR) respond to EGFR tyrosine kinase inhibitors, but drug resistance invariably emerges. To elucidate mechanisms of acquired drug resistance, we performed systematic genetic and histological analyses of tumor biopsies from 37 patients with drug-resistant non-small cell lung cancers (NSCLCs) carrying EGFR mutations. All drug-resistant tumors retained their original activating EGFR mutations, and some acquired known mechanisms of resistance including the EGFR T790M mutation or MET gene amplification. Some resistant cancers showed unexpected genetic changes including EGFR amplification and mutations in the PIK3CA gene, whereas others underwent a pronounced epithelial-to-mesenchymal transition. Surprisingly, five resistant tumors (14%) transformed from NSCLC into small cell lung cancer (SCLC) and were sensitive to standard SCLC treatments. In three patients, serial biopsies revealed that genetic mechanisms of resistance were lost in the absence of the continued selective pressure of EGFR inhibitor treatment, and such cancers were sensitive to a second round of treatment with EGFR inhibitors. Collectively, these results deepen our understanding of resistance to EGFR inhibitors and underscore the importance of repeatedly assessing cancers throughout the course of the disease.
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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.