Farnesyltransferase inhibitors: an overview of the results of preclinical and clinical investigations.
This article presents an overview of preclinical studies and clinical trials of a number of independently derived farnesyltransferase inhibitors (FTIs). Potential targets and biological modes of action of FTIs are discussed, and the results of clinical trials are summarized. The significant efficacy of FTIs as single or combined agents in preclinical studies stands in contrast with only moderate effects in clinical Phase II-III trials. These results reveal a substantial gap in the understanding of the complex activity of FTIs and their interactions with cytotoxic agents. We conclude that the rational combination of FTIs with other therapies, taking into account the biological activities of the individual agents, may improve the clinical results obtained with FTIs.
Brunner
Thomas B
TB
Department of Radiation Oncology, University of Pennsylvania, Philadelphia 19104-6072, USA.
Hahn
Stephen M
SM
Gupta
Anjali K
AK
Muschel
Ruth J
RJ
McKenna
W Gillies
WG
Bernhard
Eric J
EJ
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D051231:Farnesyltranstransferase; D006801:Humans
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase