Biochemical analysis of EGFR exon20 insertion variants insASV and insSVD and their inhibitor sensitivity.

ABSTRACT: Somatic mutations in the epidermal growth factor receptor (EGFR) are a major cause of non-small cell lung cancer. Among these structurally diverse alterations, exon 20 insertions represent a unique subset that rarely respond to EGFR tyrosine kinase inhibitors (TKIs). Therefore, there is a significant need to develop inhibitors that are active against this class of activating mutations. Here, we conducted biochemical analysis of the two most frequent exon 20 insertion variants, V769_D770insASV (insASV) and D770_N771insSVD (insSVD) to better understand their drug sensitivity and resistance. From kinetic studies, we found that EGFR insASV and insSVD are similarly active, but have lower K_{m, ATP} values compared to the L858R variant, which contributes to their lack of sensitivity to 1

SUBMITTER: Zhao H 

PROVIDER: S-EPMC11551396 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature