Farnesyltransferase inhibitors as anticancer agents: current status
- Curr Opin Investig Drugs. 2003 Dec;4(12):1428-35.
- 1. 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.
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.