Prostate Cancer: Translational and Emerging Therapies

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ISBN: 9780849371851 | 0849371856
Cover: Hardcover
Copyright: 10/4/2006

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Scientists have reached a critical point in the development of new therapies for prostate cancer. The information gleaned from the Human Genome Project, alongside the emergence of new technologies for the use of genetic data has expanded the physician's understanding of disease progression and widened his armamentarium for prostate cancer prevention and control. This expertly-written reference thoroughly analyzes the scientific principles and methodologies behind the most recent translational therapies and provides the necessary context, data, and studies for practitioners to select appropriate candidates for treatment and effectively apply new therapies in clinical practice.

Preface

iii

Contributors

xiii

1. The Molecular Pathogenesis and Pathophysiology of Prostate Cancer

(26)

William G. Nelson and Angelo M. De Marzo Introduction

(26)

Anatomy and Function of the Human Prostate

(2)

The Cellular Origin of Prostate Cancer

(1)

Genetic Susceptibility to Prostate Cancer

(2)

Epidemiology of Prostate Cancer

(1)

Inflammation and Prostate Cancer

(1)

Somatic Genome Changes in Prostate Cancer Cells

(3)

Gene Expression Changes in Prostate Cancer

(1)

Prostate Cancer Progression to Metastasis

(1)

Conclusions

(1)

References

(14)

2. Targeted Therapies for Cancer: Definitions and Attributes

(12)

Edward A. Sausville

Empirical vs. Targeted Agents for Cancer

(2)

Qualification of Cancer Targets

(1)

Agent/Target Discovery Strategies

(1)

Pathogenic Targets: Issues

(1)

Ontogenic Targets: Issues

(1)

Pharmacological Targets: Issues

(1)

Stromal Targets: Issues

(1)

Targeted Therapeutics: Differences In Development Strategy

(3)

Special Issues with Prostate Cancer

(1)

References

(2)

3. Novel Biomarkers for Disease Diagnosis, Prognosis, and Prediction

(20)

James V. Tricoli

Introduction

(1)

A Brief History of Prostate Cancer Diagnostics

(1)

Genes and Proteins Correlating with Prostate Cancer

(1)

Criteria for Biomarker Selection

(4)

Prostate Cancer Biomarkers of Interest

(5)

Future Directions

(1)

References

(8)

4. The Endothelin Pathway and its Modulation in Prostate Cancer

(16)

Antonio Jimeno and Michael Carducci

Introduction

(1)

The Endothelin Axis

(5)

Leading Compound in Cancer: Atrasentan

(5)

Other Compounds Undergoing Evaluation in Cancer: ZD4054

(1)

Conclusions

(2)

Summary

(1)

References

(4)

5. Targeting Extracellular Molecules in Prostate Cancer—Mechanisms to Inhibit Entry into the Cell-Signaling Abyss

(16)

Susan F. Slovin

Introduction

(1)

Potential Role of Cluster-Defined Molecules

(2)

PSCA—What Role does it Play as a Cell

Surface Molecule?

(1)

Mediators of Receptor Tyrosine Kinase Pathways

(2)

Platelet-Derived Growth Factor as a Target for Therapy

(1)

Inhibitors of PDGFR

(1)

Targets of Immunologic Recognition: Enhancing immunogenicity Through Vaccines by Enhancing T cell function

(1)

Studies in Men

(1)

Manipulation of the T Cell—Can Changing Expression of Cell Surface Molecules Affect Function?

(1)

Conclusions

(1)

References

(6)

6. Immunologic Approaches to Prostate Cancer

(12)

Lawrence Fong and Eric J. Small

Introduction

(1)

Detecting Responses to Immunotherapy

(1)

Prostate Antigens Recognized by T-Cells

(2)

Prostate Antigens Targeted by Antibodies

(2)

Tumor Vaccines Utilizing Prostate Cancer as a Source of Antigen

(1)

Cytokine Therapy

(1)

Immunomodulatory Treatment

(1)

Future Directions

(1)

References

(4)

7. Gene Therapy and Novel Clinical Trial Design

103

(24)

Henry T. Tsai and Jonathan W. Simons

Introduction

103

(1)

Gene Vector

104

(8)

Strategies in PCA Gene Therapy

112

(3)

Combined Modalities

115

(1)

Novel Clinical Trial Design

116

(5)

Future Directions

121

(1)

References

121

(6)

8. Angiogenesis Inhibitors in Prostate Cancer

127

(16)

William D. Figg, Michael C. Cox, Tania Alachalabi, and William L. Dahut

Introduction

127

(1)

Biologic Control of Angiogenesis

127

(1)

Proangiogenic Factors

128

(1)

Hypoxia Inducible Factor-1

128

(1)

Angiopoietin

128

(1)

Platelet-Derived Growth Factor

128

(1)

Vascular Endothelial Growth Factor

129

(1)

Prostate Cancer and the Dependence on Angiogenesis

130

(1)

Anti-angiogenic Therapy for Prostate Cancer

131

(1)

TNP-470

131

(1)

Carboxytriamidazole (CAI)

132

(1)

SU5416

132

(1)

SU101

132

(1)

2-Methoxyestradiol (Panzam, 2ME2)

132

(1)

Imatinib

132

(1)

Bevacizumab (rhuMab.VEGF)

133

(1)

Thalidomide

133

(1)

Single-Agent Thalidomide

134

(1)

Thalidomide in Combination with Anticancer Agents

134

(1)

Summary and Future Directions

135

(1)

References

135

(8)

9. What Antisense Oligonucleotides Have Promise in Prostate Cancer

143

(20)

Kim N. Chi and Martin E. Gleave

Introduction

143

(1)

Antisense Oligonucleotides

143

(3)

ASOs in Prostate Cancer

146

(8)

Summary

154

(1)

References

155

(8)

10. Novel Approaches to Androgen Receptor Blockade

163

(16)

Ingo K. Mellinghoff

Introduction

163

(1)

The Structural Basis of AR Function

163

(2)

Activation of AR Signaling

165

(2)

Mechanisms of Hormone-refractory Prostate Cancer Growth

167

(3)

Therapeutic Implications

170

(1)

References

171

(8)

11. Can Post-Transcription Modifiers Change the Course of Prostate Cancer?

179

(16)

David Z. Qian and Roberto Pili

Introduction

179

(1)

Targeting MRNA

179

(3)

Targeting Protein Synthesis

182

(1)

Targeting Protein Modification

183

(7)

Conclusions and Future Perspectives

190

(1)

References

191

(4)

12. Telomere Targeting Agents

195

(14)

Angelika M. Burger and Lloyd R. Kelland

Introduction

195

(5)

Telomerase and Telomeres in Prostate Cancer Development

200

(2)

TTA and Prostate Cancer

202

(3)

Future and Clinical Perspectives

205

(1)

References

206

(3)

13. Expanding the Role of EGFR Inhibitors in Prostate Cancer

209

(14)

Srikala S. Sridhar and Malcolm J. Moore

Introduction

209

(1)

EGFRs and Their Ligands

209

(2)

EGFRs and Prostate Cancer

211

(1)

Targeting the EGFR Family in Prostate Cancer

212

(1)

Tyrosine Kinase Inhibitors

212

(3)

Monoclonal Antibodies

215

(2)

Discussion

217

(1)

References

218

(5)

14. Bone-Directed Therapy in Prostate Cancer: Rationale and Novel Approaches

223

(14)

Colby L. Eaton, Kate D. Linton, and Freddie C. Hamdy

Abstract

223

(1)

Primary Considerations in the Evaluation of New Treatments in Prostate Cancer

223

(1)

Treatment of Established Bone Metastases: Targeting the "Vicious Cycle"

224

(5)

Prevention of Metastasis: Targeting the Establishment of Bone Metastases

229

(4)

Concluding Remarks

233

(1)

References

233

(4)

15. Inhibiting the Proteasome in Advanced Prostate Cancer

237

(8)

Robert Dreicer

Overview of the Proteasome and Its Function

237

(1)

Bortezomib

237

(1)

Inhibiting the Proteasome in Prostate Cancer

238

(1)

Clinical Experience of Bortezomib in Prostate Cancer

239

(1)

Docetaxel + Bortezomib

240

(2)

Summary

242

(1)

References

242

(3)

16. Hsp90: A Target for Prostate Cancer Therapy

245

(12)

David B. Solit, Howard I. Scher, and Neal Rosen

Introduction

245

(1)

AR Stability and Activity Are Regulated by HsP90

245

(1)

HsP90 as a Target for Cancer Therapy: Basis for a Therapeutic Index

246

(3)

Clinical Experience with 17-AAG

249

(1)

Novel HsP90 Inhibitors That Bind the N-Terminal ATP Pocket

250

(1)

HsP90 Inhibitors That Bind the C-Terminal Domain

251

(1)

HDAC Inhibitors

251

(1)

Conclusions

251

(1)

References

252

(5)

17. Vitamin D Analogs and Their Role in Prostate Cancer

257

(24)

Tomasz M. Beer and Anne Myrthue

Introduction

257

(1)

Epidemiology of Vitamin D and Prostate Cancer

257

(1)

Mechanisms of Antineoplastic Activity in Preclinical Systems

258

(3)

Vitamin D in Combination with Other Antineoplastic Agents in Preclinical Models

261

(1)

Clinical Trials of Calcitriol in Prostate Cancer

262

(4)

Calcitriol Analogs

266

(2)

Conclusions

268

(1)

References

268

(13)

18. Other Novel Therapies

281

(10)

Arif Hussain and Richard Schraeder

Introduction

281

(1)

Epothilones

281

(3)

Satraplatin

284

(2)

Conclusion

286

(1)

References

287

(4)

19. Molecular Imaging, Clinical Trial Design, and the Development of Emerging Therapies for Metastatic Prostate Cancer

291

(24)

Michael J. Morris, Neeta Pandit-Taksar, Chaitanya Divgi, Steven Larson, and Howard I. Scher

Introduction

291

(1)

Prostate Cancer, Standard Imaging, and Clinical Trial Design

292

(4)

Tracers That Demonstrate Metabolism and Growth

296

(6)

Imaging Individual Proteins Relevant to Prostate Cancer

302

(3)

Summary and Future Directions

305

(1)

References

306

(9)

Index

315

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Prostate Cancer: Translational and Emerging Therapies

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Table of Contents

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Prostate Cancer: Translational and Emerging Therapies

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