BRAF signaling and targeted therapies in melanoma

Hematol Oncol Clin North Am. 2009 Jun;23(3):529-45, ix. doi: 10.1016/j.hoc.2009.04.001.

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

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Benzenesulfonates / pharmacology
  • Benzenesulfonates / therapeutic use
  • Clinical Trials as Topic
  • Drug Delivery Systems*
  • Drugs, Investigational / pharmacology
  • Drugs, Investigational / therapeutic use
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Genes, ras
  • Humans
  • Melanoma / drug therapy
  • Melanoma / enzymology*
  • Melanoma / genetics
  • Mice
  • Mice, Nude
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mutation
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Niacinamide / analogs & derivatives
  • Phenylurea Compounds
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / physiology*
  • Pyridines / pharmacology
  • Pyridines / therapeutic use
  • Signal Transduction / drug effects
  • Sorafenib
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Benzenesulfonates
  • Drugs, Investigational
  • Neoplasm Proteins
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Pyridines
  • Niacinamide
  • Sorafenib
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinase Kinases