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Departments of Radiation Oncology [T. B. B., S. M. H., A. K. G., W. G. M., E. J. B.] and Pathology and Laboratory Medicine [R. J. M.], University of Pennsylvania, Philadelphia, Pennsylvania 19104-6072
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.
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