This volume brings together the key research issues in clinical and laboratory science relating to metastasis in prostate cancer. Coverage ranges from the most fundamental aspects of the molecular biology of metastasis, to the patient in the clinic. The therapeutic approaches range from conventional drug design to immunogene therapy. Prostate cancer is an area of intense research effort, and this book provides a window on contemporary research in this important area.

Zusammenfassung
Without metastasis, prostate cancer would be both tolerable and treatable. The high incidence of indolent and organ confined disease is testament to this sweeping generalisation. Equally, if molecular markers of metastatic spread can be identified, then the choice of treatment for many patients would be easier and more radical, even curative. However, should prevention and treatment of the primary tumors prove difficult or impossible, then a knowledge of the phenotype of advanced metastatic tumors should allow us to target these lesions for destruction by conventional (drug based) or more innovative means such as gene and/or immunotherapy (1). The process of metastasis has been reviewed many times (e. g. , 2) and has been subdivided for ease of analysis into a number of discrete stages (see Figure 1). It has been suggested that at least 10 separate genetic 2. ECM degradation: migration MMP ; Integrin ; TIMP 3. Intravasation MMP TIMP 1. Cellular independence 4. Transport Adhesion loss and evasion (E Cadherin ) of host immune system MHCClass1 ICAM-1 to block T cell receptor 5. Arrest of movement: endothelial adhesion CD44 or switch 6. Extravasation to colonise new site 7. Proliferation at Laminin R distant site to form Integrin switch METASTASIS Figure 1. Stages in prostate cancer metastasis. Basic processes in tumor metastases are indicated in the boxes with some key changes in gene expression indicated at each stage by the solid arrows.

Inhalt

Chapter 1: Introduction: Metastasis as a Therapeutic Target
Richard J. Ablin and Malcolm D. Mason

Chapter 2: The Natural History of Prostate Cancer
David F. Penson and Peter C. Albertsen

Chapter 3: The Search for Genes Which Influence Prostate Cancer Metastasis: A Moving Target?
Norman J. Maitland

Chapter 4: Polyunsaturated Fatty Acids and Prostate Cancer Metastasis
Wen G. Jiang

Chapter 5: Role of Prostaglandin Synthesis and Cyclooxygenase-2 in Prostate Cancer and Metastasis
Alaa F. Badawi

Chapter 6: Cell Cycle Regulation
Ruchi M. Newman and Bruce R. Zetter

Chapter 7: Epithelial-Mesenchymal Molecular Interactions in Prostatic Tumor Cell Plasticity
Mary J.C. Hendrix, Jun Luo, Elisabeth A. Seftor, Navesh Sharma, Paul M. Heidger
Jr., Michael B. Cohen, Robert Bhatty, Jirapat Chungthapong, Richard E.B. Seftor, and David Lubaroff

Chapter 8: Orthotopic Metastatic Mouse Models of Prostate Cancer
Robert M. Hoffman

Chapter 9: ß-Catenin, its Binding Partners and Signalling Mechanisms: Implications in Prostate Cancer
Gaynor Davies, Gregory M. Harrison, and Malcolm D. Mason

Chapter 10: Hepatocyte Growth Factor/Scatter Factor and Prostate Cancer Metastasis
Gaynor Davies, Wen G. Jiang, and Malcolm D. Mason

Chapter 11: Matrix Degradation in Prostate Cancer
Michael J. Wilson and Akhouri A. Sinha

Chapter 12: The Biology of Bone Metastases from Prostate Cancer and the Role of Bisphosphonates
Noel W. Clarke and Herbert A. Fleisch

Chapter 13: Non-Steroidal Anti-Androgen Use as Part of Combined Androgen Blockade Therapy for Metastatic or Locally Advanced Prostate Cancer: a Review of the Evidence on Efficacy and Toxicity
Mike Shelley, Charles Bennett, Derek Nathan, and Oliver Sartor

Chapter 14: Strategies for the Implementation of Chemotherapy and Radiotherapy
Paula Scullin, Joe M. O'Sullivan, and Christopher C. Parker

Chapter15: Immuno-gene Therapy for Metastatic Prostate Cancer
Takefumi Satoh, Terry L. Timme, Yehoshua Gdor, Brian J. Miles, Robert J. Amato, Dov Kadmon, and Timothy C. Thompson

Chapter 16: Distilling the Past Envisioning the Future
Richard J. Ablin and Malcolm D. Mason