ArticleNPJ precision oncology2021
Microsecond-timescale MD simulation of EGFR minor mutation predicts the structural flexibility of EGFR kinase core that reflects EGFR inhibitor sensitivity.
Article in NPJ precision oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- From Descriptor Learning to Binding Stability: An Explainable Machine Learning Pipeline for EGFR Double-Mutant Inhibitor Discovery.International journal of molecular sciences · 2026Article
- In vitro and in silico modelling of ROS1-positive non-small cell lung cancer reveals fusion-dependent tyrosine kinase inhibitor responses.Molecular oncology · 2026Article
- Dacomitinib in Combination with chemotherapy is effective in lung adenocarcinoma with rareFrontiers in oncology · 2026Article
- Efficacy of TKIs in non-small cell lung cancer with atypical EGFR p.L747P and p.L747S mutations.Frontiers in oncology · 2026Article
- Rare mutations at EGFR L747 position: molecular characteristics and superior response to afatinib in NSCLC patients.ESMO open · 2025Article
- Landscape of cancer associated EpCAM mutations: molecular modeling, predictive insights and impact on patient survival.BMC cancer · 2025Article
- Exploring the Anticancer Potential of Lamivudine-Loaded Polymeric Nanoparticles:ACS applied bio materials · 2025Article
- apoCHARMM: High-performance molecular dynamics simulations on GPUs for advanced simulation methods.The Journal of chemical physics · 2025Article
- 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
- Case of a rare EGFR mutation LRespiratory medicine case reports · 2025Article
- A macrocyclic kinase inhibitor overcomes triple resistant mutations in EGFR-positive lung cancer.NPJ precision oncology · 2024Article
- Identification of Prognostic Markers and Potential Therapeutic Targets using Gene Expression Profiling and Simulation Studies in Pancreatic Cancer.Current computer-aided drug design · 2024Article
- The treatment of patients with non-small cell lung cancer carrying uncommonTranslational cancer research · 2023Review
- Structure-Guided Strategies of Targeted Therapies for Patients withBiomolecules · 2023Review
- Durable response to afatinib rechallenge in a long-term survivor of non-small cell lung cancer harboring EGFR L858R and L747V mutations.Thoracic cancer · 2022Article
- Novel Calcium-Binding Ablating Mutations Induce Constitutive RET Activity and Drive Tumorigenesis.Cancer research · 2022Article
- Systematic analysis and molecular profiling of EGFR allosteric inhibitor cross-reactivity across the proto-oncogenic ErbB family kinases by integrating dynamics simulation, energetics calculation and biochemical assay.European biophysics journal : EBJ · 2022Article
- The Lifted Veil of Uncommon EGFR Mutation p.L747P in Non-Small Cell Lung Cancer: Molecular Feature and Targeting Sensitivity to Tyrosine Kinase Inhibitors.Frontiers in oncology · 2022Article
- Case Report: Dacomitinib is effective in lung adenocarcinoma with rare EGFR mutation L747P and brain metastases.Frontiers in oncology · 2022Article
- Anisotropic Electrostatic Interactions in Coarse-Grained Water Models to Enhance the Accuracy and Speed-Up Factor of Mesoscopic Simulations.The journal of physical chemistry. B · 2021Article
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 1 country.
Funding
Abstract
Approximately 15-30% of patients with lung cancer harbor mutations in the EGFR gene. Major EGFR mutations (>90% of EGFR-mutated lung cancer) are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs). Many uncommon EGFR mutations have been identified, but little is known regarding their characteristics, activation, and sensitivity to various EGFR-TKIs, including allosteric inhibitors. We encountered a case harboring an EGFR-L747P mutation, originally misdiagnosed with EGFR-del19 mutation using a routine diagnostic EGFR mutation test, which was resistant to EGFR-TKI gefitinib. Using this minor mutation and common EGFR-activating mutations, we performed the binding free energy calculations and microsecond-timescale molecular dynamic (MD) simulations, revealing that the L747P mutation considerably stabilizes the active conformation through a salt-bridge formation between K745 and E762. We further revealed why several EGFR inhibitors, including the allosteric inhibitor, were ineffective. Our computational structural analysis strategy would be beneficial for future drug development targeting the EGFR minor mutations.
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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.