4.5 Article

Acquired Resistance Mechanism of EGFR Kinase Domain Duplication to EGFR TKIs in Non-Small Cell Lung Cancer

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

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Summary: Understanding oncogenic variants at a mechanistic level helps in the development and optimization of treatment strategies. The study reveals the prevalence of ERBB family KDDs in multiple human cancers, and shows that EGFR-KDD functions through different dimerization modes, with its activity being maximally inhibited by blocking both intra- and inter-molecular dimerization. In conclusion, these findings define a new model of EGFR dimerization and provide important insights for the treatment of EGFR-KDD.

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