Discovery of a novel third-generation EGFR inhibitor and identification of a potential combination strategy to overcome resistance.

ABSTRACT:

Background

Non-small cell lung cancer (NSCLC) patients with activating EGFR mutations initially respond to first-generation EGFR inhibitors; however, the efficacy of these drugs is limited by acquired resistance driven by the EGFR ^T790M mutation. The discovery of third-generation EGFR inhibitors overcoming EGFR ^T790M and their new resistance mechanisms have attracted much attention.

Methods

We examined the antitumor activities and potential resistance mechanism of a novel EGFR third-generation inhibitor in vitro and in vivo using ELISA, SRB assay, immunoblotting, flow cytometric analysis, kinase array, qRT-PCR and tumor xenograft models. The clinical effect on a patient was evaluated by computed tomography scan.

Results

We identified compound ASK

SUBMITTER: Zhang T 

PROVIDER: S-EPMC7218543 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature