Targeting farnesyltransferase: is Ras relevant?

Farnesyltransferase inhibitors (FTIs) are a novel class of cancer therapeut ics that were developed to block the localization and thereby the activity of oncogenic Pas protein. Preclinical studies have established that FTIs ar e nontoxic yet capable of reversing malignant phenotypes. However, there is growing evidence that inhibition of Ras may not be crucial and that the an titransforming properties of FTIs are based at least in pan 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.