Genetic and drug perturbation of components in the NFkB signaling pathway in 11-18 cells

ABSTRACT: Through the study of EGFR-mutant lung adenocarcinoma we show that NFkB signaling is rapidly engaged by EGFR oncogene inhibition to promote tumor cell persistence and therapy resistance. Unexpectedly, we found that EGFR oncogene inhibition induced an EGFR-TRAF2-RIP1-IKK complex that stimulated an NFkB-mediated transcriptional survival program. We identified a direct pharmacologic NFkB inhibitor, PBS-1086, that suppressed this adaptive survival program and increased both the magnitude and duration of initial EGFR TKI response in cellular and in vivo tumor models, including a novel patient-derived NSCLC xenograft. These findings unveil NFkB as a critical adaptive survival mechanism engaged in response to EGFR oncogene inhibition and identify PBS-1086 as a promising NFkB inhibitor to eliminate

ORGANISM(S): Homo sapiens

SUBMITTER: Saurabh Asthana 

PROVIDER: E-GEOD-65420 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress