Working together: Farnesyl transferase inhibitors and statins block protein prenylation.
Farnesyl transferase inhibitors (FTIs) have so far proved to have limited value as single agents in clinical trials. This PharmSight will focus on the use of a novel group of FTIs that are most effective in vitro when used in combination with the "statin" class of anti-hypercholesterolemic agents, which also block protein prenylation. We recently showed that these novel FTIs in combination with lovastatin reduce Ras prenylation and induce an apoptotic response in malignant peripheral nerve sheath cells. The combination of statins with these new FTIs may produce profound synergistic cytostatic and cytotoxic effects against a variety of tumors and other proliferative disorders. Since statins are well tolerated in the clinic, we suggest that this combination approach should be tested in in vivo models.
Wojtkowiak
Jonathan W
JW
Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan.
Gibbs
Richard A
RA
Mattingly
Raymond R
RR