The potential of farnesyltransferase inhibitors as cancer chemotherapeutics

Annu Rev Pharmacol Toxicol. 1997:37:143-66. doi: 10.1146/annurev.pharmtox.37.1.143.

Abstract

Mutant ras oncogenes and alterations in the mitogenic signaling pathways that they regulate are associated with a wide variety of solid tumors and leukemias for which existing chemotherapeutics have limited utility. Of the possible approaches to inhibit Ras function, much attention has focused on a posttranslational modification, farnesylation, which is required for the subcellular localization of Ras to the plasma membrane and is critical to Ras cell-transforming activity. Inhibitors of the enzyme that catalyzes Ras farnesylation, farnesyl-protein transferase (FPTase), have been developed. These compounds inhibit the tumorigenic phenotypes of ras-transformed cells and human tumor cells in cell culture and in animal models. Moreover, FPTase inhibitors have not demonstrated toxicity to normal cells in culture or to normal tissues in mice. FPTase inhibitors are among the first small molecule compounds designed from studies of oncogenes that might serve as novel cancer chemotherapeutics.

Publication types

  • Review

MeSH terms

  • Alkyl and Aryl Transferases*
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Cell Transformation, Neoplastic / drug effects
  • Enzyme Inhibitors / therapeutic use*
  • Farnesyltranstransferase
  • Genes, Regulator / drug effects
  • Genes, ras / drug effects
  • Humans
  • Mice
  • Neoplasms, Experimental / drug therapy
  • Protein Prenylation / drug effects
  • Transferases / antagonists & inhibitors*
  • Transferases / genetics
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Transferases
  • Alkyl and Aryl Transferases
  • Farnesyltranstransferase