The Raf signal transduction cascade as a target for chemotherapeutic intervention in growth factor-responsive tumors

Pharmacol Ther. 2000 Dec;88(3):229-79. doi: 10.1016/s0163-7258(00)00085-1.


This review focuses on the Ras-Raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signal transduction pathway and the consequences of its unregulation in the development of cancer. The roles of some of the cell membrane receptors involved in the activation of this pathway, the G-protein Ras, the Raf, MEK and ERK kinases, the phosphatases that regulate these kinases, as well as the downstream transcription factors that become activated, are discussed. The roles of the Ras-Raf-MEK-ERK pathway in the regulation of apoptosis and cell cycle progression are also analyzed. In addition, potential targets for pharmacological intervention in growth factor-responsive cells are evaluated.

Publication types

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

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Membrane / physiology
  • Cell Transformation, Neoplastic*
  • Growth Substances / pharmacology*
  • Humans
  • Ligands
  • Mitogen-Activated Protein Kinase Kinases / pharmacology*
  • Mitogen-Activated Protein Kinases / pharmacology*
  • Proto-Oncogene Proteins c-raf / drug effects*
  • Proto-Oncogene Proteins c-raf / physiology*
  • Signal Transduction / physiology
  • Up-Regulation
  • ras Proteins / physiology


  • Antineoplastic Agents
  • Growth Substances
  • Ligands
  • Proto-Oncogene Proteins c-raf
  • Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • ras Proteins