ArticleNature communications2021
Structure-function analysis of oncogenic EGFR Kinase Domain Duplication reveals insights into activation and a potential approach for therapeutic targeting.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- A nomogram prediction model for brain metastases in patients with lung adenocarcinoma.Oncology letters · 2026Article
- Integrative structural and dynamics studies of epidermal growth factor receptor (EGFR).Experimental & molecular medicine · 2026Review
- ErbB family receptor dimerization dynamics and dysregulation via long-term single-molecule imaging.Cell · 2026Article
- Analysis of Somatic Mutations and Immunotherapy Biomarkers in Chinese Patients With Non-Small Cell Lung Cancer During 2019-2024: A Retrospective Study.Health science reports · 2026Article
- The role of kinase domain dimerization in EGFR activation.Structure (London, England : 1993) · 2026Article
- Disruption of the intramolecular interaction between human lung cancer-related EGFR kinase domain and carboxy-terminal tail by intra-Tyr1016 phosphorylation or extra-peptidic competitors.Journal of molecular modeling · 2026Article
- Building a dynamic model for EGFR-family dimerization using quantitative, live-cell fluorescence methods.Biophysical journal · 2025Review
- DeepEGFR a graph neural network for bioactivity classification of EGFR inhibitors.Scientific reports · 2025Article
- Strategies to Overcome Resistance to Osimertinib in EGFR-Mutated Lung Cancer.International journal of molecular sciences · 2025Review
- Adjunctive diagnostic tool for histopathological classification of congenital mesoblastic nephroma based in molecular genetic findings.Journal of cancer research and clinical oncology · 2025Article
- Colorectal cancer harboring EGFR kinase domain duplication response to EGFR tyrosine kinase inhibitors.The oncologist · 2025Article
- Epidermal Growth Factor Receptor Kinase Domain Duplication in Lung Adenocarcinoma with Sensitive Response to Afatinib: A Case Report and Literature Review.Lung Cancer (Auckland, N.Z.) · 2025Article
- Comprehensive multi-omics analysis of tandem duplicator phenotypes in non-small cell lung cancer.Frontiers in medicine · 2025Article
- Phosphatidylinositol 4,5-bisphosphate drives the formation of EGFR and EphA2 complexes.Science advances · 2024Article
- Clinical and Radiographic Benefit of a Patient With Metastatic Non-Small Cell Lung Cancer Harboring anJCO precision oncology · 2024Article
- Analysis of EGFR binding hotspots for design of new EGFR inhibitory biologics.Protein science : a publication of the Protein Society · 2024Review
- HER4 is a high-affinity dimerization partner for all EGFR/HER/ErbB family proteins.Protein science : a publication of the Protein Society · 2024Article
- Recent developments in receptor tyrosine kinase inhibitors: A promising mainstay in targeted cancer therapy.Medicine in drug discovery · 2024Article
- Observational
- Revolutionizing Glioblastoma Treatment: A Comprehensive Overview of Modern Therapeutic Approaches.International journal of molecular sciences · 2024Review
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18 authors.
Funding
Abstract
Mechanistic understanding of oncogenic variants facilitates the development and optimization of treatment strategies. We recently identified in-frame, tandem duplication of EGFR exons 18 - 25, which causes EGFR Kinase Domain Duplication (EGFR-KDD). Here, we characterize the prevalence of ERBB family KDDs across multiple human cancers and evaluate the functional biochemistry of EGFR-KDD as it relates to pathogenesis and potential therapeutic intervention. We provide computational and experimental evidence that EGFR-KDD functions by forming asymmetric EGF-independent intra-molecular and EGF-dependent inter-molecular dimers. Time-resolved fluorescence microscopy and co-immunoprecipitation reveals EGFR-KDD can form ligand-dependent inter-molecular homo- and hetero-dimers/multimers. Furthermore, we show that inhibition of EGFR-KDD activity is maximally achieved by blocking both intra- and inter-molecular dimerization. Collectively, our findings define a previously unrecognized model of EGFR dimerization, providing important insights for the understanding of EGFR activation mechanisms and informing personalized treatment of patients with tumors harboring EGFR-KDD. Finally, we establish ERBB KDDs as recurrent oncogenic events in multiple cancers.
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