Preclinical and clinical evaluation of farnesyltransferase inhibitors

Curr Oncol Rep. 2003 Mar;5(2):99-107. doi: 10.1007/s11912-003-0096-5.


Farnesylation of Ras, a protooncogene that is frequently mutated in a number of malignancies, is critical for its biologic function. This observation has led to the development of several agents that inhibit farnesyltransferase, known as farnesyltransferase inhibitors (FTIs). The antiproliferative and antitumor effects of these agents have been demonstrated in preclinical and clinical studies. Interestingly, FTI activity does not necessarily rely on ras mutational status, indicating that Ras is not the only FTI target. Clinical data suggest that FTIs, alone and in combination with other agents, have antitumor activity. Further study is needed to determine the precise mechanism of FTI antitumor activity as well as how and where FTIs will be best used clinically.

Publication types

  • Review

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Benzodiazepines / pharmacology
  • Benzodiazepines / therapeutic use
  • Clinical Trials as Topic
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use*
  • Farnesyltranstransferase
  • Genes, ras / physiology
  • Humans
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use
  • Piperidines / therapeutic use
  • Pyridines / therapeutic use
  • Quinolones / pharmacology
  • Quinolones / therapeutic use


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Imidazoles
  • Piperidines
  • Pyridines
  • Quinolones
  • Benzodiazepines
  • Alkyl and Aryl Transferases
  • Farnesyltranstransferase
  • lonafarnib
  • 7-cyano-2,3,4,5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine
  • tipifarnib