Proteasome Inhibitors in Cancer Therapy
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Proteasome Inhibitors in Cancer Therapy

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A panel of leading academic and pharmaceutical investigators takes stock of the remarkable work that has been accomplished to date with proteasome inhibitors in cancer, and examines emerging therapeutic possibilities. The topics range from a discussion of the chemistry and cell biology of the proteasome and the rationale for proteasome inhibitors in cancer to a review of current clinical trials underway. The discussion of rationales for testing proteasome inhibitors in cancer models covers the role of the proteasome in NF-kB activation, the combining of conventional chemotherapy and radiation with proteasome inhibition, notably PS-341, new proteasome methods of inhibiting viral maturation, and the role of protesome inhibition in the treatment of AIDS. The authors also document the development of bortezomib (Velcade (TM)) in Phase I clinical trials and in a multicentered Phase II clinical trials in patients with relapsed and refractory myeloma.show more

Product details

  • Hardback | 313 pages
  • 175.3 x 254 x 25.4mm | 907.2g
  • Humana Press Inc.
  • Totowa, NJ, United States
  • English
  • 2004 ed.
  • XV, 313 p.
  • 1588292509
  • 9781588292506

Review quote

"Authoritative and illuminating...." - Tumorishow more

Back cover copy

Immediately upon the discovery some ten years ago that inhibition of the proteasome in cultured cells, mostly of tumor origin, caused the programmed cell death machinery to ramp up, it became imperative to investigate proteasome inhibition as a possible treatment for human cancers. In Proteasome Inhibitors in Cancer Therapy, Julian Adams, the leader in developing the field, brings together a panel of highly experienced academic and pharmaceutical investigators to take stock of the remarkable work that has been accomplished to date, and examine emerging therapeutic possibilities for proteasome inhibitors in cancer. The topics range from a discussion of the chemistry and cell biology of the proteasome and the rationale for proteasome inhibitors in cancer to a review of current clinical trials underway. The discussion of the very empirical and practical development of rationales to test proteasome inhibitors in cancer models covers the role of the proteasome in NF-kB activation, the combining of conventional chemotherapy and radiation with proteasome inhibition, notably PS-341, new proteasome methods of inhibiting viral maturation, and the role of proteasome inhibition in the treatment of AIDS. The authors also document the development of bortezomib (Velcade(TM)) through multicentered clinical trials in patients with relapsed and refractory myeloma to FDA approval, and describe how modern pharmacogenomic tools can be used to predict which patients will respond to such proteasome inhibitor therapy. Additional chapters on the proteasome's basic biochemistry review its mechanism in the cell cycle and apoptosis and suggest opportunities for using proteasome inhibitors to find additional medicinal targets. Authoritative and illuminating, Proteasome Inhibitors in Cancer Therapy makes clear that proteasome inhibition should prove a fertile area for the many future discoveries that will provide relief of suffering and extend the quality of life of patients afflicted with cancer and other debilitating diseases.show more

Table of contents

I. Cancer Drug Development Cancer Drug Development: Challenges in a Competitive Market Barry Greene and Michael Kauffman II. Chemistry and Cell Biology of the Proteasome Introduction to the Proteasome and Its Inhibitors: Biochemistry and Cell Biology Alfred L. Goldberg Structures of the Yeast Proteasome Core Particle in Complex with Inhibitors Michael Groll and Robert Huber Natural Product and Synthetic Proteasome Inhibitors Kyung Bo Kim and Craig M. Crews Other Proteasome Inhibitors Carlos Garcia-Echeverria The Proteasome in Cell-Cycle Regulation Julian Adams Proteasome Inhibition and Apoptosis Simon A. Williams and David J. McConkey The Proteasome and the COMPARE Algorithm Susan L. Holbeck and Edward A. Sausville III. Rationale for Proteasome Inhibitors in Cancer The Proteasome in Cancer Biology and Therapy Frank Pajonk and William H. McBride Radiosensitization and Proteasome Inhibition Carter Van Waes, John B. Sunwoo, William DeGraff, and James B. Mitchell Proteasome-Dependent Regulation of NF-kB Activation: Molecular Targeting of Chemotherapy Resistance James C. Cusack, Jr. Bortezomib with Taxanes Leonard Liebes, Bruce Ng, Yi-He Ling, and Roman Perez-Soler Proteasome Inhibitor Therapy in a Brain Tumor Model Jeffrey J. Olson, Geoffrey Bowers, and Zhaobin Zhang Anthracyclines and Bortezomib Robert Z. Orlowski TNF-Related Apoptosis-Inducing Ligand (TRAIL): Combination with Proteasome Inhibition For Anticancer Therapy? Thomas J. Sayers Rationale for Combining the Proteasome Inhibitor Bortezomib with Cisplatin Edward G. Mimnaugh and Leonard M. Neckers The Effects of the HIV-1 Protease Inhibitor Ritonavir on Proteasome Activity and Antigen Presentation Marcus Groettrup, Rita deGiuli, and Gunter Schmidtke Function(s) of the Ubiquitin-Proteasome System in Retrovirus Budding Ulrich Schubert IV. Clinical Trials Preclinical Development of Bortezomib (VELCADE (TM)): Rationale for Clinical Studies Julian Adams, Peter J. Elliott, and Page Bouchard Phase I Trials: Bortezomib Alone and in Combination With Standard Chemotherapies Dixie-Lee W. Esseltine and David P. Schenkein Clinical Molecular Diagnostics for Proteasome Inhibitors in Cancer Therapy Jeffrey S. Ross, Gerald P. Linette, Geoffrey S. Ginsburg, William Trepicchio, Oscar Kashala, Rebecca Mosher, Jeffrey Brown, George Mulligan, Jim Deeds, and James Stec Phase II Trials of Bortezomib for the Treatment of Multiple Myeloma Kenneth C. Anderson Indexshow more