TABLE OF CONTENTS
Acknowledgments vii

About the Author ix

How to Use This Book xi

Chapter 1 An Introduction to Cancer Cell Biology and Genetics 1

1.1 Introduction 1

1.2 DNA Damage is the Cause of Every Cancer 2

1.3 The Defining Features (Hallmarks) of Cancer Cells 15

1.4 Genetic Variation among Cancer Cells in a Single Tumor 16

1.5 The Cancer Microenvironment 17

1.6 Cancer Spread/Metastasis 19

1.7 Cancer Stem Cells 23

1.8 Obstacles That Prevent us from Curing Cancer 24

1.9 Final Thoughts 28

Chapter 2 Introducing Targeted Cancer Treatments 33

2.1 Introduction 34

2.2 Monoclonal Antibodies 36

2.3 Kinase Inhibitors 48

2.4 Final Thoughts 60

Chapter 3 Treatments That Block Proteins Involved in Cell Communication 65

3.1 Introduction 65

3.2 Introducing Growth Factor Receptors 67

3.3 Drugs That Target EGFR 75

3.4 Drugs That Target HER2 81

3.5 Drugs That Block Other Growth Factor Receptors 85

3.6 Introduction to Signaling Pathways as a Target for Cancer Therapy 86

3.7 Targeting the MAPK Signaling Pathway 87

3.8 Targeting the PI3K/AKT/mTOR Signaling Pathway 94

3.9 Targeting the JAK-STAT Pathway 100

3.10 Final Thoughts 103

Chapter 4 Drugs That Target: Angiogenesis, Fusion Proteins, PARP, Hedgehog Signaling, and CDKs 111

4.1 Angiogenesis Inhibitors: Introduction 112

4.2 Drugs That Block Fusion Proteins: Bcr-Abl, ALK, RET, and ROS1 122

4.3 PARP Inhibitors 127

4.4 Hedgehog Pathway Inhibitors 134

4.5 Cyclin-Dependent Kinase (CDK) Inhibitors 139

4.6 Final Thoughts 145

Chapter 5 Immunotherapies for Cancer 151

5.1 Introduction 152

5.2 A Bit About Cancer and the Immune System 154

5.3 Checkpoint Inhibitors 160

5.4 Adoptive Cell Transfer 168

5.5 Modified Bi-specific Antibodies 175

5.6 Therapeutic Cancer Vaccines 176

5.7 The Future of Immunotherapy 181

Chapter 6 Targeted Treatments for Common Solid Tumors 187

6.1 Introduction 188

6.2 Targeted Treatments for Breast Cancer 188

6.3 Targeted Treatments for Prostate Cancer 200

6.4 Targeted Treatments for Lung Cancer 204

6.5 Targeted Treatments for Bowel Cancer 214

6.6 Targeted Treatments for Malignant Melanoma Skin Cancer 220

6.7 Targeted Treatments for Kidney Cancer 225

6.8 Targeted Treatments for Head and Neck Cancer 231

6.9 Targeted Treatments for Brain Tumors 235

6.10 Targeted Treatments for Bladder Cancer 236

6.11 Targeted Treatments for Pancreatic Cancer 240

6.12 Final Thoughts 244

Chapter 7 Targeted Treatments for Hematological Cancers 259

7.1 Introduction 259

7.2 A Bit About Hematological Cancers 260

7.3 Antibody-Based Treatments That Target CD Antigens 274

7.4 Drugs That Block B Cell Receptor Signaling 287

7.5 Bcr-Abl Inhibitors 292

7.6 Drugs That Block the Proteasome 294

7.7 Thalidomide and its Derivatives 297

7.8 JAK2 Inhibitors 298

7.9 Bcl-2 Inhibitors 299

7.10 FLT3 and KIT Inhibitors 301

7.11 IDH2 Inhibitors 304

7.12 CAR-Modified T Cell Therapy 304

7.13 Final Thoughts 304

Appendix 313

Glossary of Terms 315

Index 329