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mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt.
Stimulation of the insulin and insulin-like growth factor I (IGF-I) receptor activates the phosphoinositide-3-kinase/Akt/mTOR pathway causing pleiotropic cellular effects including an mTOR-dependent… Expand
Comprehensive Molecular Characterization of Human Colon and Rectal Cancer
To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and… Expand
BRAF mutation predicts sensitivity to MEK inhibition
The kinase pathway comprising RAS, RAF, mitogen-activated protein kinase kinase (MEK) and extracellular signal regulated kinase (ERK) is activated in most human tumours, often through… Expand
Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion.
Drug resistance presents a challenge to the treatment of cancer patients. Many studies have focused on cell-autonomous mechanisms of drug resistance. By contrast, we proposed that the tumour… Expand
Mutational Landscape of Metastatic Cancer Revealed from Prospective Clinical Sequencing of 10,000 Patients
Tumor molecular profiling is a fundamental component of precision oncology, enabling the identification of genomic alterations in genes and pathways that can be targeted therapeutically. The… Expand
RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)
Activated RAS promotes dimerization of members of the RAF kinase family. ATP-competitive RAF inhibitors activate ERK signalling by transactivating RAF dimers. In melanomas with mutant BRAF(V600E),… Expand
Akt Forms an Intracellular Complex with Heat Shock Protein 90 (Hsp90) and Cdc37 and Is Destabilized by Inhibitors of Hsp90 Function*
- A. Basso, D. Solit, G. Chiosis, Banabihari Giri, P. Tsichlis, N. Rosen
- Biology, Medicine
- The Journal of Biological Chemistry
- 18 October 2002
Hsp90 is a chaperone required for the conformational maturation of certain signaling proteins including Raf, cdk4, and steroid receptors. Natural products and synthetic small molecules that bind to… Expand
V600EBRAF is associated with disabled feedback inhibition of RAF–MEK signaling and elevated transcriptional output of the pathway
- C. Pratilas, B. Taylor, +4 authors N. Rosen
- Chemistry, Medicine
- Proceedings of the National Academy of Sciences
- 17 March 2009
Tumors with mutant BRAF and those with receptor tyrosine kinase (RTK) activation have similar levels of phosphorylated ERK, but only the former depend on ERK signaling for proliferation. The… Expand
OncoKB: A Precision Oncology Knowledge Base.
PURPOSE With prospective clinical sequencing of tumors emerging as a mainstay in cancer care, there is an urgent need for a clinical support tool that distills the clinical implications associated… Expand
Molecular Determinants of Response to Anti-Programmed Cell Death (PD)-1 and Anti-Programmed Death-Ligand 1 (PD-L1) Blockade in Patients With Non-Small-Cell Lung Cancer Profiled With Targeted…
- H. Rizvi, F. Sanchez-Vega, +29 authors M. Hellmann
- Journal of clinical oncology : official journal…
- 16 January 2018
Purpose Treatment of advanced non-small-cell lung cancer with immune checkpoint inhibitors (ICIs) is characterized by durable responses and improved survival in a subset of patients. Clinically… Expand