Farnesyl transferase inhibitors as anticancer agents

P. Haluska, G. K. Dy, A. A. Adjei

Research output: Contribution to journalArticlepeer-review

141 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1685-1700
Number of pages16
JournalEuropean Journal of Cancer
Volume38
Issue number13
DOIs
StatePublished - Jan 1 2002

Keywords

  • BMS-214662
  • Farnesyl transferase inhibitors
  • R115777
  • Ras
  • Rho B
  • SCH66336
  • Signal transduction

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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