Farnesyltransferase inhibitors

In the past year, clinical studies of the farnesyl transferase inhibitors (FTIs) have focused almost exclusively on hematologic malignancies, where efficacy continues to be demonstrated. In solid tumors, studies continue in breast cancer. These agents, which inhibit the post-translational modification of a large number of small G-proteins involved in cell signaling and cytoskeletal organization, are now known not to specifically inhibit Ras proteins. After over half a decade of clinical testing, the utility of these agents in the therapy of human malignancy remains to be defined. However, basic and translational studies over the past year have contributed to our understanding of the determinants of response to these agents, as well as mechanisms of resistance. With these insights, ongoing clinical studies will hopefully define the role of these agents in our anti-cancer armamentarium in the coming year.