Farnesyltransferase Inhibitors in Cancer Therapy

1. Front Matter

   Pages i-xii

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2. Signal Transduction Pathways

   • Paul Workman

   Pages 1-20

3. The Biochemistry of Farnesyltransferase and Geranylgeranyltransferase I

   • Chih-Chin Huang, Carol A. Fierke, Patrick J. Casey

   Pages 21-36

4. Structures of Protein Farnesyltransferase

   • Stephen B. Long, Lorena S. Beese

   Pages 37-48

5. Peptidomimetic-Based Inhibitors of Farnesyltransferase

   • David Knowles, Jiazhi Sun, Saul Rosenberg, Saïd M. Sebti, Andrew D. Hamilton

   Pages 49-64

6. 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 et al.

   Pages 65-70

7. Development of Farnesyltransferase Inhibitors as Potential Antitumor Agents

   • Veeraswamy Manne, Frank Lee, Ning Yan, Craig Fairchild, William C. Rose

   Pages 71-86

8. Tricyclic Farnesyl Protein Transferase Inhibitors

   • W. Robert Bishop, James J.-K. Pai, Lydia Armstrong, Marguerite B. Dalton, Ronald J. Doll, Arthur Taveras et al.

   Pages 87-101

9. Histidylbenzylglycinamides

   • Judith S. Sebolt-Leopold, Daniele M. Leonard, W. R. Leopold

   Pages 103-114

10. 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 et al.

    Pages 115-144

11. Genetic Analysis of FTase and GGTase I and Natural Product Farnesyltransferase Inhibitors

    • Fuyuhiko Tamanoi, Keith Del Villar, Nicole Robinson, MeeRhan Kim, Jun Urano, Wenli Yang

    Pages 145-157

12. Effects of Farnesyltransferase Inhibitors on Cytoskeleton, Cell Transformation, and Tumorigenesis

    • George C. Prendergast

    Pages 159-169

13. Prenyltransferase Inhibitors as Radiosensitizers

    • Eric J. Bernhard, Ruth J. Muschel, Elizabeth Cohen-Jonathan, Gilles Favre, Andrew D. Hamilton, Saïd M. Sebti et al.

    Pages 171-195

14. Farnesyltransferase and Geranylgeranyltransferase I Inhibitors as Novel Agents for Cancer and Cardiovascular Diseases

    • Saïd M. Sebti, Andrew D. Hamilton

    Pages 197-219

15. Protein Prenylation in Trypanosomatids

    • Michael H. Gelb, Frederick S. Buckner, Kohei Yokoyama, Junko Ohkanda, Andrew D. Hamilton, Lisa Nguyen et al.

    Pages 221-232

16. Early Clinical Experience with Farnesyl Protein Transferase Inhibitors

    • Amita Patnaik, Eric K. Rowinsky

    Pages 233-249

17. Phase I Trial of Oral R115777 in Patients with Refractory Solid Tumors

    • Gary R. Hudes, Jessie Schol

    Pages 251-254

18. Farnesyltransferase and Geranylgeranyltransferase Inhibitors

    • Adrienne D. Cox, L. Gerard Toussaint III, James J. Fiordalisi, Kelley Rogers-Graham, Channing J. Der

    Pages 255-273

19. Back Matter

    Pages 275-280

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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.

• biochemistry
• cancer
• cancer therapy
• cardiovascular disease
• cell
• chemistry
• development
• drugs
• medicinal chemistry
• radiation
• research
• screening
• tumorigenesis

• H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, USA

  Saïd M. Sebti

• Department of Chemistry, Yale University, New Haven, USA

  Andrew D. Hamilton

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