Farnesyltransferase Inhibitors in Cancer Therapy (Cancer Drug Discovery and Development)

Cutting-edge researchers describe their efforts to design, synthesize, and evaluate the biological activities of farensyltransferase inhibitors (FTIs); geranylgeranyltransferase inhibitors (GGTIs) are also discussed as potential anticancer drugs. 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. 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. 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. The recent explosion of knowledge gained from genes capable of causing cancer have opened up new avenues for designing anticancer drugs. This volume describes the efforts of several groups in the design and evaluation of these inhibitors. Farnesyltransferase and geranylgeranyltransferase inhibitors have remarkable potential for the treatment of cancer, cardiovascular disease, and a wide range of other disorders. Edited By Said M. Sebti And Andrew Hamilton. Includes Bibliographical References And Index.