Farnesyltransferase inhibitors: novel anticancer mechanisms and new therapeutic applications.
The development of farnesyltransferase inhibitors (FTIs) has been one of the most active areas of anticancer drug development for the past ten years. Numerous potent FTIs have been developed and extensively evaluated in preclinical model biological systems. Emphasis is given here to the discovery of new, more potent FTIs, and in particular to the results seen with agents currently being evaluated in clinical trials. The emerging, surprising differences between the proposed and actual anticancer mechanisms of the FTIs are discussed. Recent indications that the phenomenon of protein prenylation has broad therapeutic implications, beyond the potential anticancer applications of the FTIs, are presented. Finally, other components of the cellular prenylation or posttranslational modification machinery may prove to be therapeutic targets, and recent discoveries in this area are summarized.
Gibbs
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Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, Wayne State University, Detroit, MI 48202, USA. rag@wizard.pharm.wayne.edu