ArticleeLife2021
Structural basis of the effect of activating mutations on the EGF receptor.
Article in eLife, 2021. 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
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.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Structure-guided discovery and evaluation of an EGFR L858R-targeting peptide with antiproliferative activity against ovarian cancer cells.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- EGFR Mutations and Tyrosine Kinase Inhibitors: Structural Insights and Therapeutic Advances.ACS omega · 2026Review
- Lineage plasticity: a new dilemma in lung cancer treatment.Molecular biology reports · 2026Review
- Deciphering the Structural Basis of Allosteric Inhibition of Mutant Epidermal Growth Factor Receptor and Identification of Novel Inhibitors.Computational and structural biotechnology journal · 2026Article
- Exploring the mutational spectrum of key kinase genes PIK3CA, BRAF, EGFR, ALK and ROS1 in oral squamous cell carcinoma.BMC cancer · 2025Article
- STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes Exon 20-Mutant Dynamic Protein States and Achieves Unique Mutant Selectivity Across Human Cancer Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Article
- A molecular dynamics protocol for rapid prediction of EGFR overactivation and its application to the rare mutations S768I, S768N, D761N.Computational and structural biotechnology journal · 2025Article
- Biochemical analysis of EGFR exon20 insertion variants insASV and insSVD and their inhibitor sensitivity.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Entropy drives the ligand recognition in G-protein-coupled receptor subtypes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Linking ATP and allosteric sites to achieve superadditive binding with bivalent EGFR kinase inhibitors.Communications chemistry · 2024Article
- Approximating Projections of Conformational Boltzmann Distributions with AlphaFold2 Predictions: Opportunities and Limitations.Journal of chemical theory and computation · 2024Article
- The current landscape, advancements, and prospects in the treatment of patients with EGFR exon 20 insertion mutations warrant scientific elucidation.Frontiers in oncology · 2024Review
- 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
- Targeting HER3 to overcome EGFR TKI resistance in NSCLC.Frontiers in immunology · 2023Review
- Exploring the conformational dynamics and thermodynamics ofOpen life sciences · 2023Article
- A New View of Activating Mutations in Cancer.Cancer research · 2022Article
- Biochemical and structural basis for differential inhibitor sensitivity of EGFR with distinct exon 19 mutations.Nature communications · 2022Article
- Molecular mechanism of allosteric modulation for the cannabinoid receptor CB1.Nature chemical biology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations within the kinase domain of the epidermal growth factor receptor (EGFR) are common oncogenic driver events in non-small cell lung cancer. Although the activation of EGFR in normal cells is primarily driven by growth-factor-binding-induced dimerization, mutations on different exons of the kinase domain of the receptor have been found to affect the equilibrium between its active and inactive conformations giving rise to growth-factor-independent kinase activation. Using molecular dynamics simulations combined with enhanced sampling techniques, we compare here the conformational landscape of the monomers and homodimers of the wild-type and mutated forms of EGFR ΔELREA and L858R, as well as of two exon 20 insertions, D770-N771insNPG, and A763-Y764insFQEA. The differences in the conformational energy landscapes are consistent with multiple mechanisms of action including the regulation of the hinge motion, the stabilization of the dimeric interface, and local unfolding transitions. Overall, a combination of different effects is caused by the mutations and leads to the observed aberrant signaling.
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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.