Quinacrine Overcomes Resistance to Erlotinib by Inhibiting FACT, Nuclear Factor-kappa B and Cell Cycle Progression in Non-Small Cell Lung Cancer

ABSTRACT: Erlotinib is a tyrosine kinase inhibitor (TKI) that is approved as a second-line monotherapy in patients with advanced non-small cell lung cancer (NSCLC). In these patients, erlotinib prolongs survival but its benefit remains modest since many tumors express wild-type EGF receptor (wtEGFR) lacking a TKI-sensitizing mutation, develop a second-site EGFR mutation, e.g., EGFR-L858R/T790M, or activate an alternate receptor tyrosine kinase, e.g., through MET amplification. To test potential drug combinations that could improve the efficacy of erlotinib, we combined erlotinib with quinacrine, which inhibits the FACT (facilitates chromatin transcription) complex that is required for nuclear factor-κB (NF-κB) transcriptional activity. In A549 (wtEGFR), H1975 (EGFR-L858R/T790M) and H1993 (MET amplif

ORGANISM(S): Homo sapiens

SUBMITTER: Stark George 

PROVIDER: S-ECPF-GEOD-57422 | biostudies-other |

REPOSITORIES: biostudies-other