ArticleProceedings of the National Academy of Sciences of the United States of America2022
Allele-specific activation, enzyme kinetics, and inhibitor sensitivities of EGFR exon 19 deletion mutations in lung cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
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Who cites it
24 citing papers in PubMed, 25 citations in OpenAlex.
- CRISPR-Scan: Cas13a Mismatch Tolerance Enabled Ultra-Multiplexed Detection of Same-Site Indels in Acute Myeloid Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Predicting Oncogenic Mutants of Epidermal Growth Factor Receptor in Lung Cancer by Molecular Dynamics Simulation with Machine Learning.ACS omega · 2026Article
- Article
- Structure-based classification for differential tyrosine kinase inhibitors efficacy of EGFR exon 19 deletions in non-small cell lung cancer.Science China. Life sciences · 2026Article
- Article
- Targeting cancer expressed EGFR with a humanized monoclonal antibody.Scientific reports · 2026Article
- LAPTM4B Confers Resistance to EGFR-TKIs by Suppressing the Proteasomal Degradation of ATP1A1 in Non-small Cell Lung Cancer.International journal of biological sciences · 2026Article
- Building a dynamic model for EGFR-family dimerization using quantitative, live-cell fluorescence methods.Biophysical journal · 2025Review
- Saturation profiling of drug-resistant genetic variants using prime editing.Nature biotechnology · 2025Article
- Simultaneous EGFR mutation detection using a sensitive dual-target biosensor based on 3D hollow carbon nanosphere synergy with circular bipedal DNA walkers.Mikrochimica acta · 2025Article
- Evaluation of the role of EGFR exon 19 747-750 deletion mutation and plasma amino acid profile in the development of lung cancer.Molecular biology reports · 2024Article
- HER4 is a high-affinity dimerization partner for all EGFR/HER/ErbB family proteins.Protein science : a publication of the Protein Society · 2024Article
- CoHIT: a one-pot ultrasensitive ERA-CRISPR system for detecting multiple same-site indels.Nature communications · 2024Article
- First-line Osimertinib for Lung Cancer With Uncommon EGFR Exon 19 Mutations and EGFR Compound Mutations.JTO clinical and research reports · 2024Article
- Approximating Projections of Conformational Boltzmann Distributions with AlphaFold2 Predictions: Opportunities and Limitations.Journal of chemical theory and computation · 2024Article
- RELAY, Erlotinib Plus Ramucirumab in Untreated,JTO clinical and research reports · 2024Article
- Exploring acenocoumarol and silodosin in non-small cell lung cancer: Insights into EGFR-linked signaling mechanisms.F1000Research · 2024Article
- Acquired Secondary HER2 Mutations Enhance HER2/MAPK Signaling and Promote Resistance to HER2 Kinase Inhibition in Breast Cancer.Cancer research · 2023Article
- Approximating conformational Boltzmann distributions with AlphaFold2 predictions.bioRxiv : the preprint server for biology · 2023Article
- EGFR exon 19 insertion EGFR-K745_E746insIPVAIK and others with rare XPVAIK amino-acid insertions: Preclinical and clinical characterization of the favorable therapeutic window to all classes of approved EGFR kinase inhibitors.Lung cancer (Amsterdam, Netherlands) · 2023Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Oncogenic mutations within the epidermal growth factor receptor (EGFR) are found in 15 to 30% of all non-small-cell lung carcinomas. The term exon 19 deletion (ex19del) is collectively used to refer to more than 20 distinct genomic alterations within exon 19 that comprise the most common EGFR mutation subtype in lung cancer. Despite this heterogeneity, clinical treatment decisions are made irrespective of which EGFR ex19del variant is present within the tumor, and there is a paucity of information regarding how individual ex19del variants influence protein structure and function. Herein, we identified allele-specific functional differences among ex19del variants attributable to recurring sequence and structure motifs. We built all-atom structural models of 60 ex19del variants identified in patients and combined molecular dynamics simulations with biochemical and biophysical experiments to analyze three ex19del mutations (E746_A750, E746_S752 > V, and L747_A750 > P). We demonstrate that sequence variation in ex19del alters oncogenic cell growth, dimerization propensity, enzyme kinetics, and tyrosine kinase inhibitor (TKI) sensitivity. We show that in contrast to E746_A750 and E746_S752 > V, the L747_A750 > P variant forms highly active ligand-independent dimers. Enzyme kinetic analysis and TKI inhibition experiments suggest that E746_S752 > V and L747_A750 > P display reduced TKI sensitivity due to decreased adenosine 5'-triphosphate
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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.