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Cellular Plasticity and Heterogeneity of EGFR Mutant Lung Cancer

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Yale University New Haven United States

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Phenotypic changes have been observed in EGFR mutant lung cancers that become resistant to targeted therapies. This grant aims to test the hypothesis that LUAD cells can transdifferentiate upon TKI treatment and to determine the cellular and molecular mechanisms that regulate this process. We proposed to trace the cellular origin of EGFR mutant SCLC in genetically engineered mouse models by using lineage tracing to test whether EGFR mutant LUAD cells can transdifferentiate along the neuroendocrine lineage and to establish the molecular mechanisms that cause TKI resistance in EGFR mutant SCLCs. To date, we have made progress towards generating mouse models for the proposed lineage tracing experiments and have begun genomic studies of pre- and post-treatment EGFR mutant tumors that transformed to SCLC following TKI treatment.

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Technical Report,01 Sep 2014,31 Aug 2016



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Approved For Public Release;

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