Prostate Cancer (eBook)

Foreword 6
Preface 10
Contents 12
Contributors 14
Histopathology and Molecular Biology of Prostate Atrophy 17
1. INTRODUCTION 17
2. CLASSIFICATION OF FOCAL ATROPHY IN THE PROSTATE 18
3. HISTOLOGICAL MAPPING STUDIES 18
4. MOLECULAR BIOLOGY OF PROSTATE ATROPHY 25
5. SUMMARY AND CONCLUSIONS 29
REFERENCES 30
Epigenetic Gene Silencing in Prostate Cancer 33
1. INTRODUCTION 33
2. EPIGENETIC PROCESSES IN PHYSIOLOGY AND CANCER PATHOPHYSIOLOGY 34
3. ABNORMALITIES IN EPIGENETIC GENE SILENCING DURING PROSTATE CANCER INITIATION AND PROGRESSION 42
4. CGI HYPERMETHYLATION AS A MOLECULAR BIOMARKER FOR PROSTATE CANCER 45
5. EPIGENETIC GENE SILENCING AS A TARGET FOR PROSTATE CANCER PREVENTION AND TREATMENT 53
REFERENCES 56
Inherited Genetic Changes in Prostate Cancer 69
1. INTRODUCTION 69
2. WHAT EVIDENCE EXISTS FOR FAMILIAL CLUSTERING OF PROSTATE CANCER? 70
3. IS PROSTATE CANCER A HERITABLE DISEASE? 71
4. HAS AN HPC GENE BEEN IDENTIFIED? 74
5. ARE COMMON VARIANTS ASSOCIATED WITH PROSTATE CANCER RISK? 75
6. CAN TUMOR SUPPRESSOR GENES DOUBLE AS PROSTATE CANCER RISK FACTORS? 79
7. SUMMARY 81
REFERENCES 82
Prostate Molecular Oncogenesis 87
1. INTRODUCTION 87
2. CYTOGENETICS OF PROSTATE CANCER 89
3. EPIGENETIC CHANGES THAT PREDISPOSE TO PROSTATE CANCER 90
4. GENETIC CHANGES OF PROSTATE EPITHELIAL CELL TRANSFORMATION 91
5. SUMMARY 99
ACKNOWLEDGMENTS 99
REFERENCES 99
Somatic Genetic Changes in Prostate Cancer 115
1. INTRODUCTION 115
2. ANDROGEN RECEPTOR 116
3. ANDROGEN RECEPTOR AND PROSTATE CANCER 118
4. FUTURE DIRECTIONS 131
5. SUMMARY 133
REFERENCES 133
Androgen Receptor in Prostate Cancer Progression 145
1. INTRODUCTION 145
2. THE AR AND ITS ROLE IN PROSTATE FUNCTION 146
3. CELL CYCLE REGULATORS AND PROSTATE CANCER 147
4. THE AR AND PROSTATE CANCER CELL PROLIFERATION/ APOPTOSIS 148
5. THE AR AND PROSTATE CANCER INVASION/METASTASIS 151
6. COX-2 AND THE AR IN PROSTATE CANCER 155
7. SUMMARY 156
REFERENCES 156
Epigenetic Modification and Acetylation of Androgen Receptor Regulate Prostate Cellular Growth 163
1. INTRODUCTION 163
2. ANDROGEN RECEPTOR DEACETYLATION 171
3. CONCLUSIVE REMARK AND PERSPECTIVE 175
ACKNOWLEDGMENTS 175
REFERENCES 175
Estrogen Receptor a and b in the Regulation of Normal and Malignant Prostate Epithelium 179
1. INTRODUCTION: HISTORICAL PERSPECTIVE 180
2. DISCOVERY OF ESTROGEN RECEPTORS 180
3. CREATION OF KNOCKOUT MOUSE MODELS 182
4. TESTOSTERONE–5 -DIHYDROTESTOSTERONE– 5 -ANDROSTANE-3 , 17 -DIOL (3 ADIOL) PATHWAY 183
5. ERS AND PROSTATIC EPITHELIUM 184
6. PROSTATE CANCER PREVENTION TRIAL FROM ER POINT OF VIEW 186
7. ERS AND PROSTATIC STROMA 188
8. ESTROGEN IMPRINTING OF PROSTATE 189
9. SELECTIVE ER MODULATORS 191
10. SUMMARY 192
ACKNOWLEDGMENTS 192
REFERENCES 193
Estrogen Action in Normal Prostate Epithelium and in Prostate Cancer 197
1. INTRODUCTION 197
2. ESTROGENS IN THE MALE AND EFFECTS ON THE PROSTATE GLAND 198
3. PROSTATE STEROID RECEPTORS 200
4. RECEPTOR MECHANISMS OF ACTION 205
5. ERS IN THE PROSTATE GLAND 207
6. CONCLUSIONS 213
REFERENCES 214
Hypoxia-Inducible Factor 1 in the Angiogenesis of Prostate Cancer 225
1. INTRODUCTION 225
2. HIF: FUNCTION AND BIOLOGY 226
3. REGULATION OF HIF-1 230
4. HIF-1 AND TRANSLATIONAL RESEARCH IN PROSTATE CANCER 231
5. HIF AS THERAPEUTIC TARGET IN PROSTATE CANCER 232
6. SUMMARY 234
ACKNOWLEDGMENTS 234
REFERENCES 235
Signal Transduction by the Ras – MAP Kinase Pathway in Prostate Cancer Progression 239
1. INTRODUCTION 239
2. PROGRESSION TO ANDROGEN INDEPENDENCE 240
3. GROWTH FACTORS IN PROSTATE CANCER PROGRESSION 242
4. RAS SIGNALING 245
5. MAP KINASE SIGNALING 247
6. INTERSECTION OF KINASE SIGNALING WITH AR FUNCTION 258
7. IMPLICATIONS FOR THERAPY 261
ACKNOWLEDGMENTS 262
REFERENCES 262
Transcription Factors STAT5 and STAT3 273
1. INTRODUCTION 273
2. STAT FAMILY OF TRANSCRIPTION FACTORS 274
3. REGULATION OF GROWTH AND DIFFERENTIATION OF NORMAL AND MALIGNANT PROSTATE EPITHELIUM BY STAT5 SIGNALING PATHWAY 280
4. REGULATION OF PROSTATE CANCER CELL VIABILITY BY INTERLEUKIN- 6 – STAT3 SIGNALING PATHWAY 286
5. TRANSCRIPTION FACTORS STAT5 AND STAT3 AS THERAPEUTIC TARGET MOLECULES FOR PROSTATE CANCER 292
ACKNOWLEDGMENTS 293
REFERENCES 293
Role of PI3K–Akt and PTEN in the Growth and Progression of Prostate Cancer 307
1. INTRODUCTION 307
2. PTEN AS A NEGATIVE REGULATOR OF THE PI3K/AKT PATHWAY 308
3. DEREGULATION OF PTEN AND THE PI3K/AKT PATHWAY IN PROSTATE CANCER 311
4. FOXO PROTEINS: CRITICAL DOWNSTREAM TARGETS OF THE PI3K/ PTEN/ AKT PATHWAY 313
5. PROSTATE CANCER MOUSE MODELS WITH LOSS OF PTEN OR OVEREXPRESSION OF AKT 316
6. SUMMARY 318
ACKNOWLEDGMENTS 318
REFERENCES 318
New Perspectives in Prediction of Clinical Outcome of Prostate Cancer 325
1. INTRODUCTION 325
2. DISCOVERY OF TMPRSS2–ETS GENE FUSION PC 326
3. ETS FAMILY OF TRANSCRIPTION FACTORS AND PC 328
4. TMPRSS2 AND PC 329
5. TMPRSS2–ETS FUSION IN PC 330
6. TMPRSS2–ERG GENE FUSION 330
7. TMPRSS2–ETS GENE FUSION PC AND DISEASE PROGRESSION 332
8. SUMMARY 335
REFERENCES 335
New Directions in Radiation Therapy of Prostate Cancer 339
1. INTRODUCTION 340
2. EVOLUTION OF EXTERNAL RADIATION TECHNIQUES 342
3. THREE-DIMENSIONAL CONFORMAL RADIATION THERAPY 342
4. INTENSITY-MODULATED RADIATION THERAPY 343
5. IMAGE-GUIDED RADIATION THERAPY 344
6. USE OF ANDROGEN DEPRIVATION WITH RADIATION THERAPY OF PROSTATE CANCER 346
7. BRACHYTHERAPY OF PROSTATE CANCER 346
8. ADJUVANT RADIATION THERAPY AFTER RADICAL PROSTATECTOMY 349
9. FUTURE DIRECTIONS 349
ACKNOWLEDGMENTS 350
REFERENCES 350
The Current Knowledge of Hormonal Therapy in the Treatment of Prostate Cancer 355
1. INTRODUCTION 355
2. THE BIOLOGY OF ANDROGEN DEPRIVATION 356
3. TREATMENT APPROACHES 357
4. CONTROVERSIES 360
REFERENCES 366
Advances in Surgical Intervention of Prostate Cancer 371
1. INTRODUCTION 371
2. HISTORY 372
3. TECHNIQUES 374
4. OPERATIVE RESULTS 377
5. COMPARISON TO OPEN RADICAL PROSTATECTOMY 386
6. IMPACT OF ROBOTICS 391
7. FUTURE DIRECTIONS 392
8. SUMMARY 392
REFERENCES 393
Targeted Therapy Trials for Prostate Cancer 399
1. INTRODUCTION 399
2. GROWTH FACTOR AND GROWTH FACTOR RECEPTOR INHIBITORS 400
3. SIGNAL TRANSDUCTION PATHWAY INHIBITORS 405
4. CELL SURVIVAL PATHWAYS 407
5. ANTI-VASCULAR TARGETING AGENTS 408
6. SUMMARY 410
ACKNOWLEDGMENTS 411
CONFLICT OF INTEREST STATEMENT 411
REFERENCES 411
New Perspectives on Chemotherapy in Prostate Cancer 417
1. INTRODUCTION 417
2. CHEMOTHERAPY FOR ANDROGEN-INDEPENDENT PROSTATE CANCER 418
3. CHEMOTHERAPY IN HIGH-RISK LOCALIZED PROSTATE CANCER 434
4. SUMMARY 438
REFERENCES 438
Concluding Remarks 443
1. INTRODUCTION 443
2. PROSTATE CANCER SCREENING 445
3. THE FUTURE OF PROSTATE CANCER IMAGING 445
4. MOLECULAR CHARACTERIZATION AND NEW TREATMENTS 445
5. FUTURE SURGICAL APPROACHES 446
6. FUTURE OF RADIATION THERAPY 447
7. PROSTATE CANCER PRIMARY PREVENTION 448
8. QUALITY OF LIFE ISSUES IN PROSTATE CANCER 449
9. SUMMARY 449
REFERENCES 451
Index 455