Farnesyltransferase inhibitors as anticancer agents: current status.
Farnesyltransferase (FTase) is a major molecular target for the development of novel anticancer drugs that are designed to disrupt the aberrant signal transduction circuitry of tumor cells. The discovery more than a decade ago that farnesylation of Ras, one of the most prevalent oncoproteins in human cancers, is required for its cancer-causing activity was the initial stimulus to target FTase. However, it is now clear that yet to be identified farnesylated proteins other than Ras also play a pivotal role as targets for FTase inhibitors (FTIs). In this review, important mechanistic issues on the antiproliferative, pro-apoptotic and anti-angiogenic activities of FTIs, with an emphasis on potential FTI targets, will be discussed. Important clinical issues associated with translational aspects of hypotheses-driven clinical trials will also be discussed.
Zhu
Kuichun
K
Drug Discovery Program, H Lee Moffitt Cancer Center & Research Institute, Department of Interdisciplinary Oncology, University of South Florida College of Medicine, 12902 Magnolia Drive, Tampa, FL 33612, USA.
Hamilton
Andrew D
AD
Sebti
Saïd M
SM
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data / Q000639:trends; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051231:Farnesyltranstransferase; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase