biostudies-otherde La Motte Rouge T6253-6262https://www.ebi.ac.uk/biostudies/studies/S-ECPF-TABM-239EurocanPlatformNon-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 againsbiostudies-othertranscription profiling by arrayEurocanPlatformUnknown67Cancer researchHomo sapiensAraujo NPierron GArmand JPRobert Tde La Motte Rouge TLazar VHarel-Belan AKroemer GOlaussen KAPinna GZermati YWong TWGalluzzi LHarper FSoria JCTasdemir ERipoche HDessen PfalseTranscription profiling of non-small cell lung carcinoma cell line H1975 treated with cisplatin or BMS-69014 a novel panHER/VEGFR inhibitorNon-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 agains2016-04-14T14:53:51Z2007 Jul2016-04-14T14:53:51Z2016-04-14T14:53:51ZS-ECPF-TABM-239E-TABM-239EFO_0003060EFO_0000322E-TABM-239