L858R/L718Q and L858R/L792H Mutations of EGFR Inducing Resistance Against Osimertinib by Forming Additional Hydrogen Bonds.

ABSTRACT: Acquired resistance to first-line treatments in various cancers both promotes cancer recurrence as well as limits effective treatment. This is true for epidermal growth factor receptor (EGFR) mutations, for which secondary EGFR mutations are one of the principal mechanisms conferring resistance to the covalent inhibitor osimertinib. Thus, it is very important to develop a deeper understanding of the secondary mutational resistance mechanisms associated with EGFR mutations arising in tumors treated with osimertinib to expedite the development of innovative therapeutic drugs to overcome acquired resistance. This work uses all-atom molecular dynamics (MD) simulations to investigate the conformational variation of two reported EGFR mutants (L858R/L718Q and L858R/L792H) that resist osimertinib.

SUBMITTER: Imam IA 

PROVIDER: S-EPMC12036761 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature