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.

Includes supplementary material: sn.pub/extras

Inhalt
1 Signal Transduction Pathways: A Goldmine for Therapeutic Targets.- 2 The Biochemistry of Farnesyltransferase and Geranylgeranyltransferase I.- 3 Structures of Protein Farnesyltransferase.- 4 Peptidomimetic-Based Inhibitors of Farnesyltransferase.- 5 Antitumor Efficacy of a Farnesyltransferase Inhibitor in Transgenic Mice.- 6 Development of Farnesyltransferase Inhibitors as Potential Antitumor Agents.- 7 Tricyclic Farnesyl Protein Transferase Inhibitors: Antitumor Activity and Effects on Protein Prenylation.- 8 Histidylbenzylglycinamides: A Novel Class of Farnesyl DiphosphateCompetitive Peptidic Farnesyltransferase Inhibitors.- 9 From Random Screening of Chemical Libraries to the Optimization of FPP-Competitive Inhibitors of Farnesyltransferase.- 10 Genetic Analysis of FTase and GGTase I and Natural Product Farnesyltransferase Inhibitors.- 11 Effects of Farnesyltransferase Inhibitors on Cytoskeleton, Cell Transformation, and Tumorigenesis: The FTI-Rho Hypothesis.- 12 Prenyltransferase Inhibitors as Radiosensitizers.- 13 Farnesyltransferase and Geranylgeranyltransferase I Inhibitors as Novel Agents for Cancer and Cardiovascular Diseases.- 14 Protein Prenylation in Trypanosomatids: A New Piggy-Back Medicinal Chemistry Target for the Development of Agents Against Tropical Diseases.- 15 Early Clinical Experience with Farnesyl Protein Transferase Inhibitors: From the Bench to the Bedside.- 16 Phase I Trial of Oral R115777 in Patients with Refractory Solid Tumors: Preliminary Results.- 17 Farnesyltransferase and Geranylgeranyltransferase Inhibitors: The Saga Continues.