Farnesyltransferase inhibitors: antineoplastic properties, mechanisms of action, and clinical prospects

Farnesyltransferase (FTase) inhibitors are among the current wave of molecu larly targeted anti-cancer agents being used to attack malignancy in a rati onal manner A large body of preclinical data indicates that FTase inhibitor s block cancer cell proliferation through both cytostatic and cytotoxic eff ects, interestingly, FTase inhibitors have rather limited effects on normal cell function, suggesting that they ma; target unique aspects of cancer ce ll pathophysiology. The development of FTase inhibitors was predicated on t he discovery that the Ras oncoproteins must be post-translationally modifie d to transform cells. However, recent work indicates that the anti-neoplast ic effects of FTase inhibitors depend on altering the post-translational mo difications of non-Ras proteins as well. In particular; a critical target p rotein that responds to FTase inhibition by blocking turner cell growth is RhoB, an endosomal Rho protein that functions in receptor trafficking. In t his review, we survey the biological foundations for the clinical developme nt of FTase inhibitors, and consider some of the latest mechanistic studies that reveal how these agents affect cellular physiology.