Anticancer Therapeutics

Adam Todd, PhD is Senior Lecturer in Pharmaceutical Public Health in the School of Pharmacy, Faculty of Medical Sciences, at Newcastle University, UK. He is registered pharmacist, and specializes in oncology and palliative care. Paul W. Groundwater, PhD is Professor of Medicinal Chemistry in the Faculty of Pharmacy at The University of Sydney, Sydney, Australia. Jason H. Gill, PhD is a Reader in Molecular Therapeutics in the School of Pharmacy, Faculty of Medical Sciences, at Newcastle University, UK.

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