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Tumor angiogenesis : from molecular mechanisms to targeted therapy / edited by Francis S. Markland, Stephen Swenson, and Radu Minea. — Weinheim : Wiley-Blackwell, 2010. – (64.86/T925t) |
Contents
Contents
Preface XV
List of Contributors XIX
Part I Introduction 1
1 Overview on Tumor Angiogenesis 3
1.1 Once upon a Time 3
1.2 A Challenge Across Two Centuries: Inhibition of Angiogenesis to Stop Tumor Growth
1.3 Clinical Implications of Angiogenesis Inhibition 5
1.4 Angiogenesis: A Novel Bridge between Malignancy and Thrombosis 6
1.5 Conclusions 9
Acknowledgments 10
References I0
Part II Mechanisms of Angiogenesis and Lymphangiogenesis 15
2 Molecular Mechanisms of Angiogenesis 17
2.1 Vessel formation
2.2 Factors That Stimulate Blood Vessel Formation 19
2.3 Molecular Targets in the Therapeutic Inhibition of Angiogenesis
2.4 Other Impediments to Antiangiogenic Therapies 24
2.5 Future Perspectives 27
References 28
3 Proangiogenic Factors 35
3.1 Introduction 35
3.2 "Classic" Proangiogenic Factors 36
3.3 "Nonclassic" New Proangiogenic Factors 40
3.4 Conclusions and Perspectives 44
Acknowledgments 45
References 45
4 The Role of Accessory Cells in Tumor Angiogenesis 53
4.1 Introduction 53
4.2 Developmental Association of Vascular Cells and Hematopoietic Ceils 55
4.3 Inflammation and Cancer 58
4.4 Hematopoietic Cells Promote Angiogenesis as an Accessory Cell Component 59
4.5 Conclusions 71
References 72
5 Comparison between Developmental and Tumor Angiogenesis 85
5.1 Introduction 85
5.2 Vascularization by Sprouting Angiogenesis 85
5.3 Intussusceptive Vascular Growth 89
5.4 Vasculogenesis and Angioblast Recruitment 90
5.5 Cooption 91
5.6 Other Mechanisms of Vasoformation 92
5.7 Developmental Angiogenesis and Tumor Angiogenesis: Similar and Different 92
Acknowledgments 93
References 93
6 Tumor Lymphangiogenesis 97
6.1 Development of Lymphatic System 97
6.2 Tumor Lymphangiogenesis 99
6.3 Role of the VEGF-C/VEGF-D/VEGFR-3 Signaling Axis in Tumor Lymphangiogenesis
6.4 Cross Talk between Angiogenesis and Lymphangiogenesis 105
6.5 Role of Other Factors 106
6.6 Lymph Node Lymphangiogenesis 110
6.7 Therapeutic Implications 110
6.8 Summary 113
References 113
Part III Signal Transduction and Angiogenesis 125
7 Integrin Involvement in Angiogenesis 127
7.1 Introduction 127
7.2 Sprouting Angiogenesis 128
7.3 Cellular Regulators of Angiogenesis 129
7.4 Molecular Regulators of Angiogenesis 130
7.5 Integrins and Angiogenesis 131
7.6 Integrin Structure 132
7.7 Integrin Binding and Bidirectional Signaling 133
7.8 Involvement of Integrins in the Initiation Phase of Angiogenesis 135
7.9 Integrin and Growth Factor Interactions in Angiogenesis 135
7.10 Integrin and Growth Factor Receptor Interactions in Angiogenesis 136
7.11 Integrin-Mediated Regulation of Cell Adhesion 137
7.12 Integrin-Mediated Regulation of Protease Expression 138
7.13 Involvement of Integrins in the Invasive Phase of Angiogenesis 139
7.14 Involvement of Integrins in Protease Activation and Cell Surface Localization
7.15 Involvement of Integrins in the Maturation Phase of Angiogenesis 141
7.16 Conclusions 142
Acknowledgments 143
References 143
8 Signaling Pathways in Tumor Angiogenesis 153
8.1 Introduction 153
8.2 VEGF Pathway 154
8.3 Delta-Notch Pathway 159
8.4 Angiopoietin-Tie Pathway 161
8.5 Ang-1 as a Promoter of Vascular Stability/Quiescence 163
8.6 TGF-fl Pathway 166
8.7 Ephrin-Eph Pathway 167
8.8 Summary and Conclusions 170
References 170
Part IV Therapeutic Approaches and Angiogenesis 179
9 Development of an Integrin-Targeted Antiangiogenic Agent 181
9.1 Toward Molecular Treatment of Cancer 182
9.2 Disintegrins as Molecular Weapons against Cancer 184
9.3 Recombinant Expression of a Venom-Derived Disintegrin 185
9.4 Functional in vitro evaluation of VN
9.5 Functional In vivo Evaluation of VN 193
9.6 Antiangiogenic Effect of LVN Therapy 196
9.7 Toxicology Studies 199
9.8 Summary 199
References 202
10 Anti-VEGF Approaches and Newer Antiangiogenic Approaches Which Are Already in Clinical Use 207
10.1 Introduction 207
10.2 Discovery of VEGF 207
10.3 Anti-VEGF Cancer Therapeutics 210
10.4 Other Anti-VEGF Approaches 214
10.5 Non-VEGF Antiangiogenic Agents in Clinical Use 216
10.6 Future Direction of Antiangiogenesis Therapies 220
References 221
11 Combination of Antiangiogenic Therapy with Other Anticancer Therapies 227
11.1 Introduction 227
11.2 Antiangiogenic Therapy and Immunomodulation 228
11.3 Anti-VEGF andAnti-EGFR/HER-2 Combinations 231
11.4 Miscellaneous Anti-VEGF Combinations 234
11.5 Antiangiogenic Therapy and Radiation Treatment 237
11.6 Challenges of Study Design for Combined Antiangiogenic Therapy 243
References 244
12 Tumor Specificity of Antiangiogenic Agents 255
12.1 Introduction 255
12.2 Tumor Specificity 256
12.3 Drug Selectivity 259
12.4 Conclusion 268
References 269
Part V Imaging and Biomarkers in Angiogenesis 275
13 In vivo Imaging of Tumor Angiogenesis 277
13.1 Introduction 277
13.2 Mechanisms of Tumor Angiogenesis 277
13.3 Imaging 278
13.4 Conclusion 291
References 291
14 Identifying Biomarkers to Establish Drug Efficacy 299
14.1Introduction 299
14.2 Pathway Analysis as a Tool to Identify Biomarkers 301
14.3 Transcriptional Profiling as a Way to Find Biomarkers 301
14.4 Finding Biomarkers through the Use of Cell Lines 303
14.5 Finding Biomarkers through the Use of Xenografts 305
14.6 Toxicity Biomarkers 308
14.7 Imaging as a Biomarker 309
14.8 Finding and Validating Biomarkers in Clinical Trials 310
14.9 Conclusions 317
References 317
Index 321
