mTOR inhibition induces compensatory, therapeutically targetable MEK activation in renal cell carcinoma

Rapamycin derivatives allosterically targeting mTOR are currently FDA approved to treat advanced renal cell carcinoma (RCC), and catalytic inhibitors of mTOR/PI3K are now in clinical trials for treating various solid tumors. We sought to investigate the relative efficacy of allosteric versus catalyt...

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Veröffentlicht in:	PloS one 2014-09, Vol.9 (9), p.e104413-e104413
Hauptverfasser:	Bailey, Sean T, Zhou, Bing, Damrauer, Jeffrey S, Krishnan, Bhavani, Wilson, Harper L, Smith, Aleisha M, Li, Mingqing, Yeh, Jen Jen, Kim, William Y
Format:	Artikel
Sprache:	eng
Schlagworte:	1-Phosphatidylinositol 3-kinase Allosteric properties Allosteric Regulation - drug effects Animals Apoptosis Apoptosis - drug effects Autophagy Biocatalysis - drug effects Biology and Life Sciences Cancer Carcinoma, Renal Cell - enzymology Carcinoma, Renal Cell - pathology Catalysis Cell activation Cell Line, Tumor Cell Proliferation - drug effects Clinical trials Crosstalk Effectiveness Enzyme Activation - drug effects Extracellular Signal-Regulated MAP Kinases - metabolism Genetic engineering Genetics Growth factors Health aspects Humans Hypoxia Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Inhibition Kidney cancer Kidney Neoplasms - enzymology Kidney Neoplasms - pathology Kinases Mechanistic Target of Rapamycin Complex 1 Mechanistic Target of Rapamycin Complex 2 Medical research Medicine and Health Sciences Metabolic pathways Mice Mitogen-Activated Protein Kinase Kinases - metabolism Molecular Targeted Therapy Multiprotein Complexes - metabolism Pharmacology Phosphorylation - drug effects Protein Kinase Inhibitors - pharmacology Proteins Proto-Oncogene Proteins c-akt - metabolism Rapamycin Renal cell carcinoma Signal Transduction - drug effects Signaling Solid tumors Subgroups TOR protein TOR Serine-Threonine Kinases - antagonists & inhibitors TOR Serine-Threonine Kinases - metabolism Tumors Von Hippel-Lindau Tumor Suppressor Protein - metabolism
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