Resistance to Irreversible EGFR Tyrosine Kinase Inhibitors through a Multistep Mechanism Involving the IGF1R Pathway

ABSTRACT: The clinical efficacy of EGFR kinase inhibitors gefitinib and erlotinib is limited by the development of drug resistance. The most common mechanism of drug resistance is the secondary EGFR T790M mutation. Strategies to overcome EGFR T790M mediated drug resistance include the use of mutant selective EGFR inhibitors, including WZ4002, or by the use of high concentrations of irreversible quinazoline EGFR inhibitors such as PF299804. In the current study we develop drug resistant versions of the EGFR mutant PC9 cell line which reproducibly develops EGFR T790M as a mechanism of drug resistance to gefitinib. Neither PF299804 resistant (PFR) or WZ4002 resistant (WZR) clones of PC9 harbor EGFR T790M. Instead, they demonstrate activated IGF1R signaling as a result of loss of expression of

ORGANISM(S): Homo sapiens

SUBMITTER: Janne Pasi 

PROVIDER: S-ECPF-GEOD-38404 | biostudies-other |

REPOSITORIES: biostudies-other