Details

<p>Preface xi</p> <p>About the Companion Website xiii</p> <p><b>1 Cancer Epidemiology 1</b></p> <p>1.1 Cancer Incidence and Mortality 1</p> <p>1.2 Childhood Cancer 4</p> <p>1.3 Global Epidemiology 5</p> <p>1.4 Cancer Survival Rates 8</p> <p>1.5 Summary and Conclusions 12</p> <p>Further Reading 12</p> <p><b>2 Cancer Histopathology 13</b></p> <p>2.1 Cancer Morphology, Phenotype, and Nomenclature 14</p> <p>2.2 Apoptosis 16</p> <p>2.3 Necrosis 22</p> <p>2.4 Autophagy and Others 23</p> <p>2.5 Summary and Conclusions 24</p> <p>Further Reading 25</p> <p><b>3 Carcinogenesis 27</b></p> <p>3.1 Initiation 27</p> <p>3.2 Promotion 29</p> <p>3.3 Progression and Environmental Carcinogenesis 30</p> <p>3.4 Cell Cycle 31</p> <p>3.5 Summary and Conclusions 33</p> <p>Further Reading 33</p> <p><b>4 Molecular Biology of Cancer 35</b></p> <p>4.1 Oncogenes: Disruptors and Instigators 36</p> <p>4.2 Cellular Oncogenes 39</p> <p>4.3 Viral Oncogenes 41</p> <p>4.4 Altered Oncogenic Products 42</p> <p>4.5 Biological Carcinogens 44</p> <p>4.6 Tumor Suppressor Genes 46</p> <p>4.7 Familial Cancers and Cancer Syndromes 50</p> <p>4.8 Summary and Conclusions 52</p> <p>Further Reading 52</p> <p><b>5 Cancer Metastasis 53</b></p> <p>5.1 Detachment from the Primary Tumor 54</p> <p>5.2 Migration of Cancer Cells from Primary Tumor 55</p> <p>5.3 Intravasation of Tumor Cells into Vessels 57</p> <p>5.4 Metastatic Transport 60</p> <p>5.5 Extravasation 61</p> <p>5.6 Growth of the Metastatic Tumor Mass 63</p> <p>5.6.1 Cancer Dormancy 63</p> <p>5.6.2 Extracellular Matrix of the Tumor Microenvironment 64</p> <p>5.6.3 Seed and Soil 65</p> <p>5.7 Summary and Conclusions 66</p> <p>Further Reading 67</p> <p><b>6 Health Professionals and Cancer Treatment 69</b></p> <p>6.1 Pathology 69</p> <p>6.2 Radiology 70</p> <p>6.3 Biopsies 72</p> <p>6.4 Surgical Treatment 73</p> <p>6.5 Oncology Pharmacy 74</p> <p>6.6 Oncology Nursing 75</p> <p>6.7 Artificial Intelligence and Healthcare 75</p> <p>6.8 Summary and Conclusions 75</p> <p>Further Reading 76</p> <p><b>7 Principles of Cancer Chemotherapy 77</b></p> <p>7.1 Staging, Treatment, and Monitoring 77</p> <p>7.2 General Types of Chemotherapy 79</p> <p>7.3 Biomarker Uses and Limitations 82</p> <p>7.4 Pharmacogenetics, Pharmacogenomics, Pharmacokinetics, Pharmacodynamics, and Personalized Medicine 86</p> <p>7.5 Summary and Conclusions 87</p> <p>Further Reading 88</p> <p><b>8 Cytotoxic Compounds 89</b></p> <p>8.1 Alkylating Agents 89</p> <p>8.2 Intercalating Agents 94</p> <p>8.3 Topoisomerase Blockers 104</p> <p>8.4 Tubulin Disruptors 109</p> <p>8.5 Summary and Conclusions 113</p> <p>Further Reading 113</p> <p><b>9 Antimetabolites and Hormonal Blockers 115</b></p> <p>9.1 Nucleic Acid Analogs 115</p> <p>9.2 Folate Analogs 118</p> <p>9.3 Amino Acid Blockers 120</p> <p>9.4 Hormone Modulators 121</p> <p>9.5 Estrogen Antagonists 124</p> <p>9.6 Aromatase Inhibitors 127</p> <p>9.7 Antiandrogens 127</p> <p>9.8 Endocrine Therapy 128</p> <p>9.9 Summary and Conclusions 129</p> <p>Further Reading 130</p> <p><b>10 Cancer Research 131</b></p> <p>10.1 Gel Electrophoresis Methods 131</p> <p>10.2 Polymerase Chain Reaction 132</p> <p>10.3 Molecular Cloning 133</p> <p>10.4 Enzyme-Linked Immunosorbent Assay, Immunohistochemistry, and Immunofluorescence 134</p> <p>10.5 Mass Spectroscopy and Proteomics 135</p> <p>10.6 Genomics, Transcriptomics, and Metabolomics 136</p> <p>10.7 Microarrays 137</p> <p>10.8 Cell Culture and Exogenous Expression Strategies 138</p> <p>10.9 Protein Expression and Targeting 141</p> <p>10.9.1 Targeting RNA. 143</p> <p>10.9.2 Targeting the Genome 145</p> <p>10.10 Animal Models 147</p> <p>10.11 Delivery Systems 149</p> <p>10.12 Resources 151</p> <p>10.13 Summary and Conclusions 152</p> <p>Further Reading 153</p> <p><b>11 Clinical Trials 155</b></p> <p>11.1 Clinical Trial Design 158</p> <p>11.2 Clinical Trials Governance and Quality Assurance 161</p> <p>11.3 Clinical Trial Ethics 166</p> <p>11.4 Clinical Trial Study Schema 168</p> <p>11.5 Measurement of Clinical Endpoints, Response, and Outcomes 169</p> <p>11.6 Local and National Organization of Clinical Trials 169</p> <p>11.7 Summary and Conclusions 173</p> <p>Further Reading 174</p> <p><b>12 Tumor Hypoxia 175</b></p> <p>12.1 Effects of Hypoxia on Chemotherapy 177</p> <p>12.2 Energy Reprogramming and the Warburg Effect 178</p> <p>12.3 Hypoxia-Inducible Factor 181</p> <p>12.4 Lactate Dehydrogenase and Carbonic Anhydrase 183</p> <p>12.5 Hypoxic Vascularization and Imaging 185</p> <p>12.6 Bioreductive Drugs 189</p> <p>12.7 Summary and Conclusions 192</p> <p>Further Reading 192</p> <p><b>13 Antiangiogenic and Antivascular Agents 193</b></p> <p>13.1 History of Antiangiogenic Chemotherapy 193</p> <p>13.2 Endogenous Integrin Blockers 195</p> <p>13.3 Matrix Metalloproteinase Inhibitors 197</p> <p>13.4 Synthetic Integrin Blockers 202</p> <p>13.5 The Return of Thalidomide 204</p> <p>13.6 Vascular Disrupting Agents 205</p> <p>13.7 Antiangiogenic Antibodies 207</p> <p>13.8 Summary and Conclusions 210</p> <p>Further Reading 210</p> <p><b>14 Protein Kinase and Ras Blockers 211</b></p> <p>14.1 Signal Transduction 211</p> <p>14.2 Receptor Tyrosine Kinase Blockers 214</p> <p>14.3 Nonreceptor Tyrosine Kinase Blockers 216</p> <p>14.4 Receptor Serine/Threonine Kinase Blockers 220</p> <p>14.5 Nonreceptor Serine/Threonine and Multiple Kinase Blockers 223</p> <p>14.6 Ras and PLC Blockers 226</p> <p>14.7 Summary and Conclusions 228</p> <p>Further Reading 228</p> <p><b>15 Modulating Global Gene and Protein Expression 231</b></p> <p>15.1 Stress Protein Inhibitors 231</p> <p>15.2 Proteasome Inhibitors 234</p> <p>15.3 Ubiquitin Ligase Inhibitors 237</p> <p>15.4 Histone Deacetylase Inhibitors 238</p> <p>15.5 DNA Methylation Inhibitors 241</p> <p>15.6 Summary and Conclusions 242</p> <p>Further Reading 243</p> <p><b>16 Stem Cells – Telomerase, Wnt, Hedgehog, Notch, and Galectins 245</b></p> <p>16.1 Telomerase Blockers 246</p> <p>16.2 Wnt Blockers 250</p> <p>16.3 Hedgehog Blockers 252</p> <p>16.4 Notch Blockers 254</p> <p>16.5 Galectin Blockers 257</p> <p>16.6 Summary and Conclusions 258</p> <p>Further Reading 258</p> <p><b>17 Immunotherapy and Oncolytic Viruses 261</b></p> <p>17.1 Immunization 264</p> <p>17.2 Immune Checkpoint Blockers 266</p> <p>17.3 Chimeric Antigen Receptor T-Cells 268</p> <p>17.4 Oncolytic Viruses 270</p> <p>17.5 Summary and Conclusions 275</p> <p>Further Reading 275</p> <p><b>18 Pharmaceutical Problems in Cancer Chemotherapy 277</b></p> <p>18.1 Manifestation of Toxicity 277</p> <p>18.2 Regimen-Related Toxicity 282</p> <p>18.3 Secondary Malignancies 283</p> <p>18.4 Drug Resistance 284</p> <p>18.4.1 Multiple Drug Resistance 284</p> <p>18.4.2 Enhanced DNA Repair 286</p> <p>18.4.3 Alteration of Drug Targets 287</p> <p>18.5 Pharmaceutical Complications 287</p> <p>18.5.1 Extravasation 288</p> <p>18.5.2 Local and National Extravasation Guidelines 290</p> <p>18.6 Phlebitis and Venous Irritation 290</p> <p>18.7 Health and Safety 291</p> <p>18.8 National Guidance on the Safe Administration of Intrathecal Chemotherapy 291</p> <p>Further Reading 292</p> <p>Index 295</p>

<p><b>GARY S. GOLDBERG, PhD,</b> is an Associate Professor at the School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA. <p><b>RACHEL AIRLEY, MRes, PhD, MRPharmS, FHEA,</b> is a Community Pharmacist and former Lecturer in Pharmacology and Cancer Sciences, Manchester, UK.

<p><b>Provides a clear and accessible summary of all stages and aspects of the discovery, design, development, validation and clinical use of anticancer drugs</b> <p>This new edition provides an update on the current state of cancer chemotherapy and clinical practice and presents new pipeline anticancer agents and promising therapeutic strategies that are emerging alongside new breakthroughs in cancer biology. Its unique approach enables students to gain an understanding of the pathological, physiological, and molecular processes governing malignancy, while also introducing the role of health professionals and scientists in the research and treatment of cancer. <p>Invaluable for its clarity and accessibility, <i>Cancer Chemotherapy: Basic Science to the Clinic, Second Edition</i> offers complete coverage of the scientific and clinical aspects of the creation, development, and administration of drugs or drug regimens used in the treatment of the disease. Chapters look at: cancer epidemiology and histopathology; carcinogenesis; current research; tumor hypoxia; antiangiogenic and antivascular agents; protein kinase and Ras blockers; new targets associated with development such as Hedgehog and Wnt signaling; stem cells; immunotherapy and oncolytic viruses; and more. <ul> <li>Presents a clear, accessible, and comprehensive approach to cancer chemotherapy from basic science to clinical practice</li> <li>Offers a major update that reflects the latest developments in personalized chemotherapy</li> <li>Provides in-depth coverage of advances in biomarker diagnostics</li> <li>Includes new chapters/sections on bioinformatics and the 'omic sciences'; pharmaceutical strategies used to achieve tumor-selective drug delivery; and cancer cell autophagy</li> <li>Combines descriptions of both clinical protocol and explanations of the drug design process in one self-contained book</li> <li>Features numerous diagrams and illustrations to enhance reader understanding</li> </ul> <p>Aimed at upper undergraduate, graduate, and medical students, <i>Cancer Chemotherapy: Basic Science to the Clinic, Second Edition</i> is also an excellent reference for health professionals, especially clinicians specializing in Clinical Oncology, and their patients who want to gain an understanding of cancer and available treatment options.

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