Review Oncologic, Endocrine & Metabolic: Inhibitors of protein farnesylation: A new approach to cancer chemotherapy

Abstract

The Ras protein functions at a critical point in the signalling pathway between extracellular growth regulatory messengers and the nuclear factors that are responsible for the initiation of cellular replication. The action of mutant, oncogenic Ras proteins is implicated in a significant fraction of human tumours. All Ras proteins appear to require post-translational lipidation for their function. The key lipidation event is the attachment of a farnesyl unit to a cysteine near the carboxyl terminus of the protein. Recently, the possibility of interfering with Ras-mediated cell transformation through inhibition of protein farnesylation has attracted significant attention. This review surveys the types of compounds that are reported to inhibit the enzyme protein farnesyltransferase and the biological effects of these compounds in vitro and in vivo.