Anticancer Therapeutics

Preface xi

Section 1: Introduction 1

1.1 The Global Burden of Cancer 3

References 11

1.2 Cancer Staging and Classification 13

1.2.1 Benign Tumour (or neoplasm) 13

1.2.2 Malignant Tumour (or cancer) 14

1.2.3 Tumour Nomenclature and Classification 14

1.2.4 Cellular Differentiation and Tumour Grade 21

1.2.5 Tumour Invasion and Metastasis 24

1.2.6 Clinical Staging of Cancer 26

References 36

1.3 Cellular and Molecular Basis of Cancer 39

1.3.1 Oncogenes 40

1.3.2 Tumour Suppressor Genes 45

1.3.3 Role of Epigenetics and Gene Promoter Regulation in Tumourigenesis 49

1.3.4 Multistage Tumourigenesis 53

1.3.5 Oncogene Addiction 54

1.3.6 Hallmarks of Cancer 55

1.3.7 Principles of Cancer Treatment 73

References 77

Section 2: The Anticancer Agents 81

2.1 Agents Which Act Directly on DNA 83

2.1.1 Nitrogen Mustards and Nitrosoureas 83

References 96

2.1.2 Temozolomide 98

References 106

2.1.3 Platinum]containing Agents 108

References 118

2.1.4 Gemcitabine 120

References 128

2.1.5 Camptothecin and Its Analogues 128

References 139

2.1.6 Podophyllotoxins 141

References 150

2.1.7 Anthracyclines 151

References 160

2.1.8 Epigenetic Targeting Agents 162

References 177

2.2 Antimetabolites 181

2.2.1 Cytarabine 181

References 183

2.2.2 Methotrexate 184

References 195

2.2.3 5]Fluorouracil 196

References 205

2.2.4 6]Mercaptopurine 206

References 210

2.3 Antimicrotubule Agents 211

2.3.1 Taxanes 211

References 224

2.3.2 Vinca Alkaloids 225

References 231

2.4 Anti]hormonal Agents 233

2.4.1 Bicalutamide 233

References 239

2.4.2 Tamoxifen 240

References 247

2.4.3 Anastrozole 248

References 254

2.5 Kinase Inhibitors 257

2.5.1 Discovery 257

2.5.2 Synthesis 262

2.5.3 Mode of Action 267

2.5.4 Mechanism of Resistance 268

2.5.5 Adverse Drug Reactions 268

References 271

Section 3: The Cancers 275

3.1 Breast Cancer 277

Key points 277

3.1.1 Epidemiology 277

3.1.2 Presentation 279

3.1.3 Diagnosis 282

3.1.4 Staging 283

3.1.5 Treatments 285

References 289

3.2 Colorectal Cancer 293

Key points 293

3.2.1 Epidemiology 293

3.2.2 Presentation 294

3.2.3 Diagnosis 296

3.2.4 Staging 298

3.2.5 Treatments 299

References 303

3.3 Leukaemia 307

Key points 307

3.3.1 Epidemiology 307

3.3.2 Presentation 310

3.3.3 Diagnosis 311

3.3.4 Staging 313

3.3.5 Treatments 314

References 319

3.4 Lung Cancer 323

Key points 323

3.4.1 Epidemiology 323

3.4.2 Presentation 327

3.4.3 Diagnosis 327

3.4.4 Staging 330

3.4.5 Treatments 330

References 337

3.5 Oesophageal Cancer 339

Key points 339

3.5.1 Epidemiology 339

3.5.2 Presentation 340

3.5.3 Diagnosis 341

3.5.4 Staging 344

3.5.5 Treatments 346

References 350

3.6 Ovarian Cancer 353

Key points 353

3.6.1 Epidemiology 353

3.6.2 Presentation 354

3.6.3 Diagnosis 356

3.6.4 Staging 357

3.6.5 Treatments 357

References 363

3.7 Pancreatic Cancer 367

Key points 367

3.7.1 Epidemiology 367

3.7.2 Presentation 368

3.7.3 Diagnosis 370

3.7.4 Staging 371

3.7.5 Treatments 373

References 375

3.8 Prostate Cancer 379

Key points 379

3.8.1 Epidemiology 379

3.8.2 Presentation 381

3.8.3 Diagnosis 382

3.8.4 Staging 384

3.8.5 Treatments 387

References 391

3.9 Skin Cancers 393

Key points 393

3.9.1 Epidemiology 393

3.9.2 Presentation 394

3.9.3 Diagnosis 395

3.9.4 Staging 396

3.9.5 Treatments 399

References 403

3.10 Testicular Cancer 405

Key points 405

3.10.1 Epidemiology 405

3.10.2 Presentation 407

3.10.3 Diagnosis 407

3.10.4 Staging 409

3.10.5 Treatments 409

References 414

Index 417