Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy?

Nat Rev Cancer. 2010 Dec;10(12):842-57. doi: 10.1038/nrc2960. Epub 2010 Nov 24.


There is now considerable and increasing evidence for a causal role for aberrant activity of the Ras superfamily of small GTPases in human cancers. These GTPases function as GDP-GTP-regulated binary switches that control many fundamental cellular processes. A common mechanism of GTPase deregulation in cancer is the deregulated expression and/or activity of their regulatory proteins, guanine nucleotide exchange factors (GEFs) that promote formation of the active GTP-bound state and GTPase-activating proteins (GAPs) that return the GTPase to its GDP-bound inactive state. In this Review, we assess the association of GEFs and GAPs with cancer and their druggability for cancer therapeutics.

Publication types

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

MeSH terms

  • Animals
  • Brefeldin A / therapeutic use
  • Drug Discovery
  • GTPase-Activating Proteins / antagonists & inhibitors*
  • GTPase-Activating Proteins / physiology
  • Guanine Nucleotide Exchange Factors / antagonists & inhibitors*
  • Guanine Nucleotide Exchange Factors / physiology
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / etiology
  • Neoplasms / metabolism
  • Proto-Oncogene Proteins / physiology
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1


  • ECT2 protein, human
  • GTPase-Activating Proteins
  • Guanine Nucleotide Exchange Factors
  • PREX1 protein, human
  • Proto-Oncogene Proteins
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1
  • TIAM1 protein, human
  • Brefeldin A