Transcription profiling of non-small cell lung carcinoma cell line H1975 treated with cisplatin or BMS-69014 a novel panHER/VEGFR inhibitor

ABSTRACT: Non-small cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) responds to EGFR tyrosine kinase inhibitors such as erlotinib. However, secondary somatic EGFR mutations (e.g. T790M) confer resistance to erlotinib. BMS-690514, a novel panHER/VEGFR inhibitor described here, exerted antiproliferative and pro-apoptotic effects on NSCLC cell lines, with prominent efficacy on H1975 cells expressing the T790M mutation. In this model, BMS-690514 induced a G1 cell cycle arrest, as well as ultrastructural hallmarks of apoptosis, mitochondrial release of cytochrome c, and activation of caspases involved in the intrinsic (e.g. caspase -2, -3, -7 and -9), but not in the extrinsic (e.g. caspase-8) pathway. Caspase inhibition conferred partial protection agains

ORGANISM(S): Homo sapiens

SUBMITTER: de La Motte Rouge T 

PROVIDER: S-ECPF-TABM-239 | biostudies-other | 2007 Jul

REPOSITORIES: biostudies-other