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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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ShRNA profiling of melanoma A375 cells stably expressing a shRNA construct for doxycycline-inducible knockdown of B-Raf (2 mg/ml Dox, antitumor efficacy of RAF inhibitor GDC-0879 involving BRAFV600E mutational status and ERK/MAPK pathway suppression

ABSTRACT: Unsupervised hierarchical clustering revealed a strong similarity in gene modulation resulting from either compound treatment or BRAF ablation mediated by RNA interference relative to DMSO-treated control samples . Experiment Overall Design: We have generated melanoma A375 cells stably expressing a shRNA construct for doxycycline-inducible knockdown of B-Raf (2 mg/ml Dox, 48h). Small molecule treatment was at 1000nM R341787, 24h.

ORGANISM(S): Homo sapiens

SUBMITTER: Peter Haverty

PROVIDER: E-GEOD-13487 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Antitumor efficacy of the novel RAF inhibitor GDC-0879 is predicted by BRAFV600E mutational status and sustained extracellular signal-regulated kinase/mitogen-activated protein kinase pathway suppression.

Hoeflich Klaus P KP Herter Sylvia S Tien Janet J Wong Leo L Berry Leanne L Chan Jocelyn J O'Brien Carol C Modrusan Zora Z Seshagiri Somasekar S Lackner Mark M Stern Howard H Choo Edna E Murray Lesley L Friedman Lori S LS Belvin Marcia M

Cancer research 20090310 7

Oncogenic activation of the BRAF serine/threonine kinase has been associated with initiation and maintenance of melanoma tumors. As such, development of pharmacologic agents to target RAF proteins or their effector kinases is an area of intense investigation. Here we report the biological properties of GDC-0879, a highly selective, potent, and orally bioavailable RAF small-molecule inhibitor. We used extracellular signal-regulated kinase (ERK)-1/2 and mitogen-activated protein kinase/ERK kinase ...[more]

PMID: 19276360

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