Intrinsic Resistance to MEK Inhibition in KRAS Mutant Lung and Colon Cancer through Transcriptional Induction of ERBB3

There are no effective therapies for the ~30% of human malignancies with mutant RAS oncogenes. Using a kinome-centered synthetic lethality screen, we find that suppression of the ERBB3 receptor tyrosine kinase sensitizes KRAS mutant lung and colon cancer cells to MEK inhibitors. We show that MEK inh...

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Veröffentlicht in:	Cell reports (Cambridge) Jg. 7; H. 1; S. 86 - 93
Hauptverfasser:	Sun, Chong, Hobor, Sebastijan, Bertotti, Andrea, Zecchin, Davide, Huang, Sidong, Galimi, Francesco, Cottino, Francesca, Prahallad, Anirudh, Grernrum, Wipawadee, Tzani, Anna, Schlicker, Andreas, Wessels, Lodewyk F.A., Smit, Egbert F., Thunnissen, Erik, Halonen, Pasi, Lieftink, Cor, Beijersbergen, Roderick L., Di Nicolantonio, Federica, Bardelli, Alberto, Trusolino, Livio, Bernards, Rene
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States Elsevier 01.04.2014
Schlagworte:	Animals Apoptosis - genetics Cell Line, Tumor Colonic Neoplasms - drug therapy Colonic Neoplasms - enzymology Colonic Neoplasms - genetics Colonic Neoplasms - pathology Drug Synergism Humans Lung Neoplasms - drug therapy Lung Neoplasms - enzymology Lung Neoplasms - genetics Lung Neoplasms - pathology MAP Kinase Kinase Kinases - antagonists & inhibitors MAP Kinase Kinase Kinases - metabolism Mice Mice, Nude Mutation Protein Kinase Inhibitors - pharmacology Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins p21(ras) ras Proteins - genetics ras Proteins - metabolism Receptor, Epidermal Growth Factor - antagonists & inhibitors Receptor, ErbB-2 - antagonists & inhibitors Receptor, ErbB-2 - metabolism Receptor, ErbB-3 - biosynthesis Receptor, ErbB-3 - genetics Receptor, ErbB-3 - metabolism RNA, Small Interfering - administration & dosage RNA, Small Interfering - genetics Xenograft Model Antitumor Assays
ISSN:	2211-1247, 2211-1247
Online-Zugang:	Volltext
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