New approaches to anticancer drug design based on the inhibition of farnesyltransferase

Mutated forms of the GTP-binding protein Ras are found in 30% of human cancers, with particularly high prevalence in colon and pancreatic carcinomas. Ras function in growth factor signaling requires post- translational farnesylation of a cysteine residue present as part of the CA₁A₂X carboxyl terminal tetrapeptide. The enzyme farnesyltransferase has become an important target for the design of potential new antitumor agents. The authors outline the major new approaches to inhibition of farnesyltransferase and describe how certain peptidomimetics have been shown to block oncogenic signaling and tumor growth in various animal models.