With the explosion of research on genes capable of causing cancer, it has become clear that mutations in the GTPase, Ras, a major regulator of cell division, are found in about 30% of all human cancers, and that farnesylation, a lipid posttranslational modification of Ras, is required for its cancer-causing activity. In Farnesyltransferase Inhibitors in Cancer Therapy, cutting-edge researchers describe their efforts to design, synthesize, and evaluate the biological activities of farnesyltransferase inhibitors (FTIs) and geranylgeranyltransferase inhibitors (GGTIs) that can be used as anticancer drugs and in cardiovascular and parasitic therapy. The authors survey in detail such inhibitors as CAAX box peptidomimetics, FPP mimics, and bisubstrate transition state analogs, and critically review their uses in combination with radiation and other cytotoxic agents, such as gemcitabine, cisplatin, and taxanes. The book also discusses the results from several phase I and II human clinical trials using a variety of FTIs, and demonstrates the design of hypothesis-driven clinical trials with proof-of-concept using biochemical endpoints.
Illuminating and richly detailed, Farnesyltransferase Inhibitors in Cancer Therapy constitutes today's standard reference for the pathbreaking use of FTIs and GGTIs in anticancer therapy and offers basic and clinical investigators a comprehensive treatment of the scientific and medical aspects of farnesyltransferase inhibitors.

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Signal Transduction Pathways: A Goldmine for Therapeutic Targets, Paul Workman. The Biochemistry of Farnesyltransferase and Geranylgeranyltransferase I, Chih-Chin Huang, Carol A. Fierke, and Patrick J. Casey. Structures of Protein Farnesyltransferase, Stephen B. Long and Lorena S. Beese. Peptidomimetic-Based Inhibitors of Farnesyltransferase, David Knowles, Jiazhi Sun, Saul Rosenberg, Saïd M. Sebti, and Andrew D. Hamilton. Antitumor Efficacy of a Farnesyltransferase Inhibitor in Transgenic Mice, Jackson B. Gibbs, Samuel L. Graham, George D. Hartman, Kenneth S. Koblan, Nancy E. Kohl, Charles Omer, Angel Pellicier, Jolene Windle, and Allen Oliff. Development of Farnesyltransferase Inhibitors as Potential Antitumor Agents, Veeraswamy Manne, Frank Lee, Ning Yan, Craig Fairchild, and William C. Rose. Tricyclic Farnesyl Protein Transferase Inhibitors: Antitumor Activity and Effects on Protein Prenylation, W. Robert Bishop, James J.-K. Pai, Lydia Armstrong, Marguerite B. Dalton, Ronald J. Doll, Arthur Taveras, George Njoroge, Michael Sinensky, Fang Zhang, Ming Liu, and Paul Kirschmeier. Histidylbenzylglycinamides: A Novel Class of Farnesyl Diphosphate-Competitive Peptidic Farnesyltransferase Inhibitors, Judith S. Sebolt-Leopold, Daniele M. Leonard, and W. R. Leopold. From Random Screening of Chemical Libraries to the Optimization of FPP-Competitive Inhibitors of Farnesyltransferase, Patrick Mailliet, Abdel Laoui, Jean-Dominique Bourzat, Marc Capet, Michel Chevé, Alain Commerçon, Norbert Dereu, Alain LeBrun, Jean-Paul Martin, Jean-François Peyronel, Christophe Salagnad, Fabienne Thompson, Martine Zucco, Jean-Dominique Guitton, Guy Pantel, Marie-Christine Bissery, Clive Brealey, Jacques Lavayre, Yves Lelièvre, Jean-François Riou, Patricia Vrignaud, Marc Duchesne, and François Lavelle. Genetic Analysis of FTase and GGTase I and Natural Product Farnesyltransferase Inhibitors, Fuyuhiko Tamanoi, Keith Del Villar, Nicole Robinson, MeeRhan Kim, Jun Urano, and Wenli Yang.Effects of Farnesyltransferase Inhibitors on Cytoskeleton, Cell Transformation, and Tumorigenesis: The FTI-Rho Hypothesis, George C. Prendergast. Prenyltransferase Inhibitors as Radiosensitizers, Eric J. Bernhard, Ruth J. Muschel, Elizabeth Cohen-Jonathan, Gilles Favre, Andrew D. Hamilton, Saïd M. Sebti, and W. Gillies McKenna. Farnesyltransferase and Geranylgeranyltransferase I Inhibitors as Novel Agents for Cancer and Cardiovascular Diseases, Saïd M. Sebti and Andrew D. Hamilton. Protein Prenylation in Trypanosomatids: A New Piggy-Back Medicinal Chemistry Target for the Development of Agents Against Tropical Diseases, Michael H. Gelb, Frederick S. Buckner, Kohei Yokoyama, Junko Ohkanda, Andrew D. Hamilton, Lisa Nguyen, Bartira Rossi-Bergmann, Kenneth D. Stuart, Saïd M. Sebti, and Wesley C. Van Voorhis. Early Clinical Experience with Farnesyl Protein Transferase Inhibitors: From the Bench to the Bedside, Amita Patnaik and Eric K. Rowinsky. Phase I Trial of Oral R115777 in Patients with Refractory Solid Tumors: Preliminary Results, Gary R. Hudes and Jessie Schol. Farnesyltransferase and Geranylgeranyltransferase Inhibitors: The Saga Continues, Adrienne D. Cox, L. Gerard Toussaint III, James J. Fiordalisi, Kelley Rogers-Graham, and Channing J. Der. Index.