Abstract
The RAS/RAF/MEK/ERK signaling pathway has emerged as a major player in the induction and maintenance of melanoma, particularly the protein kinase BRAF, mutated in approximately 44% of melanoma cases. The availability of new drugs affecting the components of this pathway and pathways that may cooperate with MAPK signaling, means that targeted therapies are fast becoming a real option in the clinical management of melanoma. The authors discuss what they learned from clinical trials using first- and second-generation inhibitors to this pathway.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use*
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Benzenesulfonates / pharmacology
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Benzenesulfonates / therapeutic use
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Clinical Trials as Topic
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Drug Delivery Systems*
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Drugs, Investigational / pharmacology
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Drugs, Investigational / therapeutic use
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / genetics
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Genes, ras
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Humans
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Melanoma / drug therapy
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Melanoma / enzymology*
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Melanoma / genetics
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Mice
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Mice, Nude
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Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinase Kinases / genetics
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Mutation
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology*
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Niacinamide / analogs & derivatives
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Phenylurea Compounds
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Protein Kinase Inhibitors / administration & dosage
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Protein Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / therapeutic use*
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Proto-Oncogene Proteins B-raf / antagonists & inhibitors
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Proto-Oncogene Proteins B-raf / genetics
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Proto-Oncogene Proteins B-raf / physiology*
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Pyridines / pharmacology
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Pyridines / therapeutic use
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Signal Transduction / drug effects
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Sorafenib
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Xenograft Model Antitumor Assays
Substances
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Antineoplastic Agents
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Benzenesulfonates
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Drugs, Investigational
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Neoplasm Proteins
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Phenylurea Compounds
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Protein Kinase Inhibitors
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Pyridines
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Niacinamide
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Sorafenib
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BRAF protein, human
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Proto-Oncogene Proteins B-raf
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Extracellular Signal-Regulated MAP Kinases
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Mitogen-Activated Protein Kinase Kinases