Modulation of plasma metabolite biomarkers of MAPK pathway with the MEK inhibitor RO4987655: pharmacodynamic and predictive potential in metastatic melanoma
نویسندگان
چکیده
AFFILIATIONS: Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London SW7 3RP, UK Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK Roche Pharmaceutical Research and Early Development, Translational Medicine Oncology, Roche Innovation Center Penzberg, Penzberg, Germany Roche Pharmaceutical Research and Early Development, Translational Medicine Oncology, Roche Innovation Center Basel, Basel Switzerland Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom F. Hoffmann-LaRoche Ltd., Diagnostics Division, DIA Biomarker Group, Basel, Switzerland
منابع مشابه
Modulation of Plasma Metabolite Biomarkers of the MAPK Pathway with MEK Inhibitor RO4987655: Pharmacodynamic and Predictive Potential in Metastatic Melanoma.
MAPK pathway activation is frequently observed in human malignancies, including melanoma, and is associated with sensitivity to MEK inhibition and changes in cellular metabolism. Using quantitative mass spectrometry-based metabolomics, we identified in preclinical models 21 plasma metabolites including amino acids, propionylcarnitine, phosphatidylcholines, and sphingomyelins that were significa...
متن کاملPhase I expansion and pharmacodynamic study of the oral MEK inhibitor RO4987655 (CH4987655) in selected patients with advanced cancer with RAS-RAF mutations.
PURPOSE This phase I expansion study assessed safety, pharmacodynamic effects, and antitumor activity of RO4987655, a pure MEK inhibitor, in selected patients with advanced solid tumor. EXPERIMENTAL DESIGN We undertook a multicenter phase I two-part study (dose escalation and cohort expansion). Here, we present the part 2 expansion that included melanoma, non-small cell lung cancer (NSCLC), a...
متن کاملEvaluation of efficacy of a new MEK inhibitor, RO4987655, in human tumor xenografts by [18F] FDG-PET imaging combined with proteomic approaches
BACKGROUND Inhibition of mitogen-activated protein kinase (MEK, also known as MAPK2, MAPKK), a key molecule of the Ras/MAPK (mitogen-activated protein kinase) pathway, has shown promising effects on B-raf-mutated and some RAS (rat sarcoma)-activated tumors in clinical trials. The objective of this study is to examine the efficacy of a novel allosteric MEK inhibitor RO4987655 in K-ras-mutated hu...
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AIMS This proof-of-concept study was designed to determine if functional, pharmacodynamic profiles relevant to targeted therapy could be derived from live human melanoma samples using a novel automated platform. METHODS A series of 13 melanoma cell lines was briefly exposed to a BRAF inhibitor (PLX-4720) on a platform employing automated fluidics for sample processing. Levels of the phosphopr...
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Background: Xanthohumol is one of the main bioactive compounds extracted from the female flowers of the hops plant (Humulus lupulus L), that has been shown in several studies to have anti-cancer effects.The MAPK/ERK pathway is one of the key pathways in the regulation of gene expression, cell growth and survival. The abnormal activation of this pathway leads to the uncontrolled cell proliferati...
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