EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors.

ABSTRACT:

Purpose

Mutant selective irreversible pyrimidine-based EGFR kinase inhibitors, including WZ4002, CO-1686, and AZD9291, are effective in preclinical models and in lung cancer patients harboring the EGFR T790M gefitinib/erlotinib resistance mutation. However, little is known about how cancers develop acquired resistance to this class of EGFR inhibitors. We sought to identify and study EGFR mutations that confer resistance to this class of agents.

Experimental design

We performed an N-ethyl-N-nitrosourea (ENU) mutagenesis screen in EGFR-mutant (sensitizing alone or with concurrent EGFR T790M) Ba/F3 cells and selected drug-resistant clones. We evaluated the sensitivity of EGFR inhibitors in models harboring drug-resistant EGFR mutations.

Results

We identified 3 major drug

SUBMITTER: Ercan D 

PROVIDER: S-EPMC4791951 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature