Farnesyl transferase inhibitors as anticancer agents

Eur J Cancer. 2002 Sep;38(13):1685-700. doi: 10.1016/s0959-8049(02)00166-1.


Protein farnesylation catalysed by the enzyme farnesyl protein transferase involves the addition of a 15-carbon farnesyl group to conserved amino acid residues at the carboxyl terminus of certain proteins. Protein substrates of farnesyl transferase include several G-proteins, which are critical intermediates of cell signalling and cytoskeletal organisation such as Ras, Rho, PxF and lamins A and B. Activated Ras proteins trigger a cascade of phosphorylation events through sequential activation of the PI3 kinase/AKT pathway, which is critical for cell survival, and the Raf/Mek/Erk kinase pathway that has been implicated in cell proliferation. Ras mutations which encode for constitutively activated proteins are found in 30% of human cancers. Because farnesylation of Ras is required for its transforming and proliferative activity, the farnesyl protein transferase inhibitors were designed as anticancer agents to abrogate Ras function. However, current evidence suggests that the anticancer activity of the farnesyl transferase inhibitors may not be simply due to Ras inhibition. This review will discuss available clinical data on three of these agents that are currently undergoing clinical trials.

Publication types

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

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Antineoplastic Agents / therapeutic use*
  • Benzodiazepines / therapeutic use
  • Cell Division
  • Clinical Trials as Topic
  • Combined Modality Therapy / methods
  • Enzyme Inhibitors / therapeutic use
  • Farnesyltranstransferase
  • Genes, ras
  • Humans
  • Imidazoles / therapeutic use
  • Neoplasms / drug therapy*
  • Neoplasms / radiotherapy
  • Piperidines / therapeutic use
  • Pyridines / therapeutic use
  • Quinolones / therapeutic use
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Imidazoles
  • Piperidines
  • Pyridines
  • Quinolones
  • Benzodiazepines
  • L 778,123
  • 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