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Proteasome Inhibitors in Cancer Therapy
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Main description:

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™) in Phase I clinical trials and in a multicentered Phase II clinical trials in patients with relapsed and refractory myeloma.


Back cover:

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™) 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.


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 García-Echeverría

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™): 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

Index


PRODUCT DETAILS

ISBN-13: 9781617374524
Publisher: Springer (Humana Press)
Publication date: November, 2010
Pages: 328
Weight: 691g
Availability: POD
Subcategories: Oncology, Pharmacology
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"Authoritative and illuminating...." - Tumori