EGFR-A763_Y764insFQEA Is a Unique Exon 20 Insertion Mutation That Displays Sensitivity to Approved and In-Development Lung Cancer EGFR Tyrosine Kinase Inhibitors.

ABSTRACT: The EGFR-A763_Y764insFQEA is a unique exon 20 insertion mutation (~5% to 6% of exon 20 insertions), which, at the structural and enzyme kinetic level, more closely resembles EGFR tyrosine kinase inhibitor (TKI)- sensitizing mutants, such as EGFR exon 19 indels and L858R. A limited number of preclinical models and clinical reports have studied the response of this mutant to EGFR TKIs. We used models of EGFR-A763_Y764insFQEA and more typical EGFR exon 20 insertion mutations to probe representative first- (gefitinib, erlotinib), second- (afatinib), third-generation (osimertinib), and in-development EGFR exon 20-specific (poziotinib, mobocertinib [TAK-788]) TKIs. We also compiled outcomes of EGFR-A763_Y764insFQEA-mutated lung cancers treated with EGFR TKIs. Cells driven by EGFR-A763_Y764insFQE

SUBMITTER: Vasconcelos PENS 

PROVIDER: S-EPMC8183979 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature