DeVita, Hellman, and Rosenberg's Cancer: Principles and Practice of Oncology

• Vincent T DeVita, Jr. MD
• Amy and Joseph Perella Professor of Medicine, Yale Comprehensive Cancer Center and Smilow Cancer Hospital at New Haven, New Haven, CT

• Theodore S Lawrence MD, PhD
• Isadore Lampe Professor and Chair, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI

• Steven A Rosenberg MD, PhD
• Chief of Surgery, National Cancer Institute, National Institutes of Health; Professor of Surgery, Uniformed Services University of the Health Sciences School of Medicine, Bethesda, MD; Professor of Surgery, George Washington University School

• Ronald A DePinho MD
• Director, Center for Applied Cancer Science, Belfer Institute for Innovative Cancer Science, Dana-Farber Cancer Institute, American Cancer Society Research Professor, Professor of Medicine and Genetics, Harvard Medical School, Boston, MA</

• Robert A Weinberg PhD
• Member, Whitehead Institute for Biomedical Research, Daniel K. Ludwig Professor of Biology, Massachusetts Institute of Technology, Cambridge, MA

• Edition: Ninth
• Product Format: Hardbound
• ISBN: 9781451105452
• Trim Size: 8.375 x 10.875
• Pages: 2800
• Pub Date: May 16, 2011
• Weight: 10.0

• ALL MEDICINE
• Hematology
• Oncology

Contributing Authors vii Preface xxvii Acknowledgments xxix PART ONE MOLECULAR BIOLOGY OF CANCER 1. The Cancer Genome . . . . . . . . . . . . . . . . . . . 2Yardena Samuels, Alberto Bardelli, and Carlos L\u00f3pez-Ot\u00edn Cancer Genes and Their Mutations 2 Identification of Cancer Genes 2 Cancer Genome Investigation: Tools and Quality Controls 2 Somatic Alteration Classes Detected by Cancer Genome Analysis 12 Pathway-Oriented Models of Cancer Genome Analysis 14 Networks of Cancer Genome Projects 16 The Genomic Landscape of Cancers 18 The Cancer Genome and the New Taxonomy of Tumors 18 Cancer Genomics and Drug Resistance 20 Perspectives of Cancer Genome Analysis 20 2. Mechanisms of Genomic Instability . . . . . . . 23David J. Gordon, David A. Barbie, Alan D. DÆAndrea, and David Pellman Basic Defenses Against Genomic Instability 23 Barriers to Genomic Instability 23 Mutations in Cancer 26 Mechanisms of Genome Destabilization in Human Tumors 29 What Causes Chromosomal Instability and Whole-Chromosome Aneuploidy? 35 Does Whole-Chromosome Aneuploidy Cause Cancer? 37 Perspectives and Implications for Cancer Therapeutics 38 3. Epigenetics of Cancer . . . . . . . . . . . . . . . . . . 41Peter A. Jones and Karin B. Michels Epigenetic Processes 41 Epigenomic Changes in Cancer 43 The Timing of Epigenetic Alterations 44 Epigenetic Biomarkers for Early Detection of Cancer 44 Epigenetic Therapies 45 Problems with Epigenetic Therapies 46 4. Telomeres, Telomerase, and Cancer . . . . . . . 48Kwok-Kin Wong, Norman E. Sharpless, and Ronald A. DePinho Telomeres and Telomerase 48 Senescence 50 Telomere Maintenance and Cancer 53 5. Receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 Cell Signaling Growth Factors and TheirLewis C. Cantley, Chris L. Carpenter, William C. Hahn, and Matthew Meyerson Signal Transduction Systems 57 Sensory Machinery: Ligands and Receptors 57 Regulation of Protein Kinases 60 Small-Molecule Second Messengers 63 Efficiency and Specificity: Formation of Multiprotein Signaling Complexes 64 Signaling Networks 66 6. Cell Cycle. . . . . . . . . . . . . . . . . . . . . . . . . . . 68Steven I. Reed Cell-Cycle Engine 68 Induction of Cell-Cycle Phase Transitions 71 Ubiquitin-Mediated Proteolysis 71 Regulation of the Cell Cycle 72 Cell Cycle and Cancer 76 MicroRNAs, the Cell Cycle, and Cancer 79 The Cell Cycle and Cancer Therapy 80 7. Mechanisms of Cell Death . . . . . . . . . . . . . . 82Vassiliki Karantza and Eileen White Apoptosis 82 Autophagy 87 Necrosis 89 8. Cancer Metabolism . . . . . . . . . . . . . . . . . . . 91Matthew G. Vander Heiden Altered Metabolism in Cancer Cells 91 Energetics of Cell Proliferation 93 Imaging Cancer Metabolism in Patients 94 Genetic Events Important for Cancer Influence Metabolism 95 Targeting Metabolism to Treat Cancer 99 9. Angiogenesis . . . . . . . . . . . . . . . . . . . . . . . 101Robert S. Kerbel and Lee M. Ellis Introduction: Origins of the Concept of Antiangiogenic Therapy for Cancer 101 Sequential Steps Involved in the Formation of Blood Vessel Capillaries in Tumors 101 Pericytes 102 Dysfunctional Nature of the Tumor Vasculature 102 Molecular Mediators of Tumor Angiogenesis: Angiogenic Stimulators and Their Receptors 103 Endogenous Inhibitors of Tumor Angiogenesis 105 A Cooperative Regulator of Tumor Angiogenesis: The Notch Receptor- DLL4 Signaling Pathway in Endothelial Cells 106 Strategies for Development of Antiangiogenic Drugs 106 Enhancement of Chemotherapy Efficacy and Other Therapeutic Modalities by Antiangiogenic Drugs 107 Resistance to Antiangiogenic Drugs or Treatments 108 Biomarkers for Tumor Angiogenesis and Antiangiogenic Therapy 109 Antiangiogenic/Anti-VEGF Drug-Based Clinical Trials 109 Looking Ahead: New Targets, New Drugs, and New Strategies for Antiangiogenic Therapy 111 10. Invasion and Metastasis . . . . . . . . . . . . . . . 113Andy J. Minn and Joan Massagu\u00e9 The Evolution and Pathogenesis of Metastasis 113 An Integrated Model for Metastasis 115 Selective Pressures at the Primary Tumor Driving Acquisition of Metastasis Functions 117 Coupling Tumorigenesis with Metastasis Initiation 119 Coupling Tumorigenesis with Metastasis Progression 121 From Metastasis Progression to Macrometastatic Colonization 122 Micro-RNAs and Metastasis 126 11. Cancer Stem Cells . . . . . . . . . . . . . . . . . . . 128Jean C. Y. Wang and John E. Dick Tumor Heterogeneity 128 Leukemia Stem Cells 129 CONTENTS xxxi Cancer Stem Cells in Solid Tumors 130 Genetic Diversity and Clonal Evolution in Cancer 133 The Origins of Cancer Stem Cells 134 Epithelial-Mesenchymal Transition 137 Cancer Stem Cells: Targeted Therapy 137 12. Biology of Personalized Cancer Medicine . . .141Raju Kucherlapati Cancer Predisposition 141 Familial Adenomatous Polyposis 141 Lynch Syndrome 142 Other Polyposis Syndromes 142 Association Studies 142 Breast Cancer 142 Early Detection 143 Tumor Classification and Patient Stratification 143 Treatment 144 Development of Resistance to Tyrosine Kinase Inhibitors 145 Alternative Mechanisms of Resistance 145 BRAF Inhibitors 146 The Future 146 Changing Face of Personalized Medicine 146 Summary 146 PART TWO ETIOLOGY AND EPIDEMIOLOGY OF CANCER Section 1: Etiology of Cancer 13. Tobacco . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 Stephen S. Hecht Epidemiology of Tobacco and Cancer 150 Tumor Induction in Laboratory Animals by Tobacco Products 152 Carcinogens in Tobacco Products 153 Overview of Mechanisms of Tumor Induction by Tobacco Products 156 Tobacco Carcinogen and Toxicant Biomarkers 157 14. Cancer Susceptibility Syndromes . . . . . . . . 161Alice Hawley Berger and Pier Paolo Pandolfi Principles of Cancer Susceptibility 161 Genetic Testing 163 Cancer Susceptibility Syndromes 164 Future Directions 170 15. DNA Viruses . . . . . . . . . . . . . . . . . . . . . . . 173Peter M. Howley, Don Ganem, and Elliott Kieff History of Viral Oncology 173 Hepadnaviruses and Hepatocellular Carcinoma 174 Papillomaviruses 176 Epstein-Barr Virus 180 KaposiÆs Sarcoma–Associated Herpesvirus 182 Human Polyomaviruses 184 16. RNA Viruses . . . . . . . . . . . . . . . . . . . . . . . 186Gary L. Buchschacher, Jr. and Flossie Wong-Staal Retroviruses: Background, Replication Cycle, and Molecular Genetics 186 Human T-Lymphotropic Virus Type 1 189 Human T-Lymphotropic Virus Type 2 190 Human Immunodeficiency Virus 190 Hepatitis C Virus 190 17. Inflammation . . . . . . . . . . . . . . . . . . . . . . . 193Giorgio Trinchieri Tumor Immune Surveillance 193 Inflammation and Tumorigenesis 194 Mechanisms of Cell Transformation and Cancer Initiation in the Inflammatory Environment 196 Inflammatory Cells and Stromal Cells in the Initiation of Neoplasia and in the Tumor Microenvironment 198 18. Chemical Factors . . . . . . . . . . . . . . . . . . . . 203Stuart H. Yuspa and Peter G. Shields The Nature of Chemical Carcinogens: Chemistry and Metabolism 203 Animal Model Systems and Chemical Carcinogenesis 205 DNA Repair Protects the Host from Chemical Carcinogens 205 Genetic Susceptibility to Chemical Carcinogenesis 205 Molecular Epidemiology, Chemical Carcinogenesis, and Cancer Risk in Human Populations 206 Polyclic Aromatic Hydrocarbons as a Model for Gene-Environment Interaction 207 19. Physical Factors . . . . . . . . . . . . . . . . . . . . . 209Mats Ljungman Ionizing Radiation 209 Ultraviolet Light 212 Radiofrequency and Microwave Radiation 214 Electromagnetic Fields 214 Asbestos 214 Nanoparticles 215 20. Dietary Factors . . . . . . . . . . . . . . . . . . . . . 217Karin B. Michels and Walter C. Willett Methodologic Challenges 217 The Role of Individual Food and Nutrients in Cancer Etiology 218 Other Foods and Nutrients 222 Dietary Patterns 224 Diet During Early Phases of Life 224 Summary 224 Limitations 2