Targeting farnesyltransferase: is Ras relevant?

Farnesyltransferase inhibitors (FTIs) are a novel class of cancer therapeutics that were developed to block the localization and thereby the activity of oncogenic Ras protein. Preclinical studies have established that FTIs are nontoxic yet capable of reversing malignant phenotypes. However, there is growing evidence that inhibition of Ras may not be crucial and that the antitransforming properties of FTIs are based at least in part upon alteration of Rho, a small GTPase which is involved in cell adhesion and cytoskeletal regulation. These recent developments are reviewed and their impact on the design of clinical trials is discussed. Copyright 1999 Harcourt Publishers Ltd.