Section Review Oncologic,Endocrine & Metabolic: Farnesyl-protein transferase inhibitors in early development

Over the last decade the underlying mechanisms that cause tu-mourigenesis are progressively being elucidated. One potential mechanism includes the participation of farnesyl-protein transferase in promoting the effects of oncogenic forms of ras. Membrane localisation of Ras is essential for ras-induced tumour formation. Farnesyl-protein transferase catalyses the attachment of farnesyl to the carboxyl terminal cysteine residue of Ras. Genetic evidence indicates that unprenylated oncogenic Ras is soluble, cannot promote tumourigenesis and is apparently not deleterious to the cell. Several inhibitors of farnesyl-protein transferase are currently being tested in animal models of tumourigenesis. This review will focus on compounds that are presently being developed by Eisai, Banyu, Bristol-Myers Squibb, Merck, Roche/Genentech/University of Texas, Schering-Plough and the University of Pittsburgh.