Targeting the Raf/MEK/ERK pathway with small-molecule inhibitors

Curr Opin Investig Drugs. 2008 Jun;9(6):614-30.


Mutations occur in some cancer cells and result in elevated expression or constitutive activation of various growth factor receptors. The Raf/MEK/ERK pathway is often activated by mutations in these growth factor receptors. This pathway is regulated by upstream Ras, which is mutated in 20 to 30% of human cancers. B-Raf is also activated by mutation, especially in melanoma and thyroid cancers. Many of the events elicited by the Raf/MEK/ERK pathway have direct effects on survival and proliferative pathways. Aberrant regulation of the Raf/MEK/ERK pathway can contribute to uncontrolled cell growth and lead to malignant transformation. The effective targeting of this pathway may result in the suppression of cell growth, and death of malignant cells. This review focuses on targeting the Raf/MEK/ERK pathway with small-molecule inhibitors for the treatment of cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors*
  • Humans
  • MAP Kinase Kinase Kinases / antagonists & inhibitors*
  • Signal Transduction / drug effects
  • Small Molecule Libraries
  • raf Kinases / antagonists & inhibitors*


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Small Molecule Libraries
  • raf Kinases
  • Extracellular Signal-Regulated MAP Kinases
  • MAP Kinase Kinase Kinases