Post-translational modifications and regulation of the RAS superfamily of GTPases as anticancer targets

Nat Rev Drug Discov. 2007 Jul;6(7):541-55. doi: 10.1038/nrd2221.


The involvement of the RAS superfamily of monomeric GTPases in carcinogenesis is increasingly being appreciated. A complex array of post-translational modifications and a highly sophisticated protein network regulate the spatio-temporal activation of these GTPases. Previous attempts to pharmacologically target this family have focused on the development of farnesyltransferase inhibitors, but the performance of such agents in cancer clinical trials has not been as good as hoped. Here, we review emerging druggable targets and novel therapeutic approaches targeting prenylation and post-prenylation modifications and the functional regulation of GDP/GTP exchange as exciting alternatives for anticancer therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Clinical Trials as Topic
  • Farnesyltranstransferase / antagonists & inhibitors
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Protein Prenylation / drug effects
  • Protein Processing, Post-Translational*
  • ras Proteins / metabolism*


  • Antineoplastic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Farnesyltranstransferase
  • ras Proteins