ArticleScience translational medicine2013
Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer.
Article in Science translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04137718 (Multicenter Observational Study for Clinicopathological Characteristics and Clinical Efficacy of Chinese Non-Small Cell Lung Cancer), which is not on this map. Cited by 300 papers, 4 of them syntheses that pooled it.
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.
Multicenter Observational Study for Clinicopathological Characteristics and Clinical Efficacy of Chinese Non-Small Cell Lung Cancer (NSCLC) Patients With Rare Driver Gene Mutation
Who cites it
300 citing papers in PubMed, 4 syntheses or guidelines pooled it, 555 citations in OpenAlex.
- Efficacy and safety of later-line targeted therapies in advanced non-small cell lung cancer with EGFR exon 20 insertion mutations: a systematic review.Frontiers in pharmacology · 2025Pooled it
- A systematic review of genetic ancestry as a risk factor for incidence of non-small cell lung cancer in the US.Frontiers in genetics · 2023Pooled it
- Therapeutic exploration of uncommon EGFR exon 20 insertion mutations in advanced non-small cell lung cancer: breaking through brambles and thorns.Journal of cancer research and clinical oncology · 2022Pooled it
- Epidemiological and clinical burden of EGFR Exon 20 insertion in advanced non-small cell lung cancer: A systematic literature review.PloS one · 2021Pooled it
- Poziotinib for EGFR exon 20-insertion NSCLC: Clinical efficacy of the phase 2 ZENITH trial and differential impact of EGFR exon 20 insertion location on sensitivity.Nature communications · 2025Trial
- Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity.Cancer cell · 2022Trial
- Erlotinib and Onalespib Lactate Focused on EGFR Exon 20 Insertion Non-Small Cell Lung Cancer (NSCLC): A California Cancer Consortium Phase I/II Trial (NCI 9878).Clinical lung cancer · 2021Trial
- Activity and Safety of Mobocertinib (TAK-788) in Previously Treated Non-Small Cell Lung Cancer withCancer discovery · 2021Trial
- Tarloxotinib Is a Hypoxia-Activated Pan-HER Kinase Inhibitor Active Against a Broad Range of HER-Family Oncogenes.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- EGFR exon 20-altered NSCLC in China: molecular heterogeneity and real-world outcomes with sunvozertinib.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Predicting Oncogenic Mutants of Epidermal Growth Factor Receptor in Lung Cancer by Molecular Dynamics Simulation with Machine Learning.ACS omega · 2026Article
- Increasing incidence and improved survival of leptomeningeal metastasis in advanced lung cancer: a 10-year real-world cohort study.Translational lung cancer research · 2026Article
- Osimertinib Resistance in EGFR-Mutated Non-Small Cell Lung Cancer: Mechanisms and Therapeutic Strategies.MedComm · 2026Review
- Review
- Resistance to EGFR Inhibitors in NSCLC: Mechanistic Insights and Emerging Therapies.International journal of molecular sciences · 2026Review
- ErbB family receptor dimerization dynamics and dysregulation via long-term single-molecule imaging.Cell · 2026Article
- The resistance landscape of EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer: molecular mechanisms and novel therapeutic strategies.Translational lung cancer research · 2026Review
- Cudratricusxanthone A Exhibits Antitumor Activities Against NSCLC Harboring EGFR L792H and G796R Triple Mutations via Regulating EGFR-ERK/AKT/STAT3 Signaling.Molecules (Basel, Switzerland) · 2026Article
- Therapeutic Advances in Non-Small Cell Lung Cancer HarboringInternational journal of molecular sciences · 2026Review
- Epidermal growth factor receptor tyrosine kinase inhibitor for the treatment of non-small cell lung cancer in the past 30 years (1997-2026).Chinese medical journal · 2026Review
240 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
24 authors at 5 institutions in 2 countries.
Funding
Abstract
Epidermal growth factor receptor (EGFR) gene mutations (G719X, exon 19 deletions/insertions, L858R, and L861Q) predict favorable responses to EGFR tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). However, EGFR exon 20 insertion mutations (~10% of all EGFR mutations) are generally associated with insensitivity to available TKIs (gefitinib, erlotinib, and afatinib). The basis of this primary resistance is poorly understood. We studied a broad subset of exon 20 insertion mutations, comparing in vitro TKI sensitivity with responses to gefitinib and erlotinib in NSCLC patients, and found that most are resistant to EGFR TKIs. The crystal structure of a representative TKI-insensitive mutant (D770_N771insNPG) reveals an unaltered adenosine triphosphate-binding pocket, and the inserted residues form a wedge at the end of the C helix that promotes the active kinase conformation. Unlike EGFR-L858R, D770_N771insNPG activates EGFR without increasing its affinity for EGFR TKIs. Unexpectedly, we find that EGFR-A763_Y764insFQEA is highly sensitive to EGFR TKIs in vitro, and patients whose NSCLCs harbor this mutation respond to erlotinib. Analysis of the A763_Y764insFQEA mutant indicates that the inserted residues shift the register of the C helix in the N-terminal direction, altering the structure in the region that is also affected by the TKI-sensitive EGFR-L858R. Our studies reveal intricate differences between EGFR mutations, their biology, and their response to EGFR TKIs.
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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.