scholarly journals Clinical outcomes of EGFR kinase domain duplication to targeted therapies in NSCLC

2018 ◽  
Vol 144 (11) ◽  
pp. 2677-2682 ◽  
Author(s):  
Jinguang Wang ◽  
Xingya Li ◽  
Xingyang Xue ◽  
Qiuxiang Ou ◽  
Xue Wu ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Targeted Therapies ◽  
Kinase Domain ◽  
Domain Duplication ◽  
Egfr Kinase

scholarly journals Structure–function analysis of oncogenic EGFR Kinase Domain Duplication reveals insights into activation and a potential approach for therapeutic targeting

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhenfang Du ◽  
Benjamin P. Brown ◽  
Soyeon Kim ◽  
Donna Ferguson ◽  
Dean C. Pavlick ◽  
...  
Keyword(s):  
Tandem Duplication ◽  
Function Analysis ◽  
Treatment Strategies ◽  
Kinase Domain ◽  
Time Resolved ◽  
Egfr Activation ◽  
Domain Duplication ◽  
Activation Mechanisms ◽  
Potential Therapeutic Intervention ◽  
Egfr Kinase

AbstractMechanistic 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.

scholarly journals Lung adenocarcinoma patient with an EGFR kinase domain duplication (KDD) and the response to icotinib

2018 ◽  
Vol 10 (5) ◽  
pp. E359-E363 ◽  
Author(s):  
You-Cai Zhu ◽  
Wen-Xian Wang ◽  
Chun-Wei Xu ◽  
Qing-He Tan ◽  
Jian-Ying Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Domain ◽  
Domain Duplication ◽  
Lung Adenocarcinoma Patient ◽  
Egfr Kinase

Abstract 867: EGFR kinase domain duplication (EGFR-KDD) is activated by asymmetric intra-molecular dimerization

2019 ◽  
Author(s):  
Zhenfang Du ◽  
Jean-Nicolas Gallant ◽  
Monica Red-Brewer ◽  
Benjamin Brown ◽  
Jonathan Sheehan ◽  
...  
Keyword(s):  
Kinase Domain ◽  
Domain Duplication ◽  
Egfr Kinase

Osimertinib confers potent binding affinity to EGFR kinase domain duplication

2019 ◽  
Vol 145 (10) ◽  
pp. 2884-2885 ◽  
Author(s):  
Rui Jin ◽  
Jie Li ◽  
Zhou Jin ◽  
Yuefei Lu ◽  
Yang W. Shao ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Kinase Domain ◽  
Domain Duplication ◽  
Egfr Kinase

scholarly journals EGFR Kinase Domain Duplication (EGFR-KDD) Is a Novel Oncogenic Driver in Lung Cancer That Is Clinically Responsive to Afatinib

2015 ◽  
Vol 5 (11) ◽  
pp. 1155-1163 ◽  
Author(s):  
Jean-Nicolas Gallant ◽  
Jonathan H. Sheehan ◽  
Timothy M. Shaver ◽  
Mark Bailey ◽  
Doron Lipson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Kinase Domain ◽  
Domain Duplication ◽  
Oncogenic Driver ◽  
Egfr Kinase

scholarly journals The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies

Cancer Cell ◽  
2006 ◽  
Vol 9 (6) ◽  
pp. 485-495 ◽  
Author(s):  
Hongbin Ji ◽  
Danan Li ◽  
Liang Chen ◽  
Takeshi Shimamura ◽  
Susumu Kobayashi ◽  
...  
Keyword(s):  
Targeted Therapies ◽  
Kinase Domain ◽  
Lung Tumorigenesis ◽  
Kinase Domain Mutations ◽  
The Impact ◽  
Egfr Kinase

scholarly journals Intramolecular Dimerization of EGFR Kinase Domain Duplication as a Novel Activation Mechanism

2017 ◽  
Vol 12 (8) ◽  
pp. S1536
Author(s):  
Z. Du ◽  
J.-N. Gallant ◽  
J. Sheehan ◽  
J. Meiler ◽  
C.M. Lovly
Keyword(s):  
Kinase Domain ◽  
Activation Mechanism ◽  
Domain Duplication ◽  
Egfr Kinase
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