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<p>Forward xiii</p> <p>Acknowledgements xv</p> <p>List of contributors xvii</p> <p><b>Section I: Development of Anticancer Therapeutics 1</b></p> <p><b>1 Exploring the Potential of Natural Products in Cancer Treatment 3<br /> </b><i>Fotini N. Lamari and Paul Cordopatis</i></p> <p>1.1 Introduction 3</p> <p>1.2 Sources 4</p> <p>1.3 Different Approaches to the Search for Bioactive Natural Products 6</p> <p>1.4 Methodologies of Lead Compound or New Drug Identification 10</p> <p>1.5 Chemoprevention – A New Area for Natural Product Research 13</p> <p>1.6 Concluding Remarks 13</p> <p><b>2 Combinatorial Approaches to Anticancer Drug Design 17<br /> </b><i>Sotiris Missailidis</i></p> <p>2.1 Introduction 17</p> <p>2.2 Combinatorial Approaches for Small Molecule Drug Design 17</p> <p>2.3 Display Technologies 21</p> <p>2.4 Aptamer Selection 23</p> <p>2.5 Conclusions 27</p> <p><b>3 Rational Approaches to Anticancer Drug Design/in silico Drug Development 29<br /> </b><i>Stefano Alcaro, Anna Artese and Francesco Ortuso</i></p> <p>3.1 Introduction 29</p> <p>3.2 Approaches to the Drug Discovery Process in Anticancer Research 31</p> <p>3.3 Ligand-based Examples 32</p> <p>3.4 Structure-based Examples 36</p> <p>3.5 Conclusions 44</p> <p><b>Section II: Anticancer Therapeutics 47</b></p> <p><b>4 Introduction to Anticancer Therapeutics 49<br /> </b><i>Teni Boulikas</i></p> <p>4.1 Problems in cancer 49</p> <p>4.2 Cancer treatments 51</p> <p>4.3 Classification of chemotherapy drugs 53</p> <p><b>5 Platinum Drugs 55<br /> </b><i>Teni Boulikas, Alexandros Pantos, Evagelos Bellis and Petros Christofis</i></p> <p>5.1 Cisplatin 55</p> <p>5.2 Lipoplatin 57</p> <p>5.3 Carboplatin 61</p> <p>5.4 Oxaliplatin 62</p> <p>5.5 Lipoxal 62</p> <p>5.6 New Platinum Compounds 64</p> <p>5.7 Cisplatin Resistance and Chemotherapy 70</p> <p><b>6 Antimicrotubule Agents 79<br /> </b><i>Iain Brown, Jay N Sangrithi-Wallace and Andrew C Schofield</i></p> <p>6.1 Taxanes 79</p> <p>6.2 Vinca Alkaloids 82</p> <p>6.3 Mechanisms of Resistance to Antimicrotubule Agents 86</p> <p><b>7 Antimetabolites in Cancer Therapy 91<br /> </b><i>Jessica Scaife and David Kerr</i></p> <p>7.1 Introduction 91</p> <p>7.2 Folate Antagonists 92</p> <p>7.3 Pyrimidine Antagonists 96</p> <p>7.4 Purine Antagonists 104</p> <p>7.5 Summary 109</p> <p><b>8 Antitumour Antibiotics 111<br /> </b><i>Manuel M. Paz</i></p> <p>8.1 Introduction 111</p> <p>8.2 Actinomycin 111</p> <p>8.3 Mitomycin c 112</p> <p>8.4 Bleomycin 115</p> <p>8.5 Anthracyclines 118</p> <p>8.6 Trabectedin (Ecteinascidin, ET-743) 121</p> <p>8.7 Camptothecins 123</p> <p>8.8 Podophyllotoxins 124</p> <p><b>9 Alkylating Agents 133<br /> </b><i>Ana Paula Francisco, Maria de Jesus Perry, Rui Moreira and Eduarda Mendes</i></p> <p>9.1 Introduction 133</p> <p>9.2 Nitrogen Mustards 133</p> <p>9.3 Methylmelamines and Ethylenimines 140</p> <p>9.4 Methylhydrazine Derivatives 141</p> <p>9.5 Alkylsulfonates 143</p> <p>9.6 Nitrosoureas 144</p> <p>9.7 Triazenes 149</p> <p><b>10 Hormone Therapies 159<br /> </b><i>George C. Zografos, Nikolaos V. Michalopoulos and Flora Zagouri</i></p> <p>10.1 Introduction 159</p> <p>10.2 Oestrogen Receptor Targeted Therapeutics 160</p> <p>10.3 Progesterone-Targeted Therapy 174</p> <p>10.4 Neuroendocrine Tumours 176</p> <p><b>11 Photodynamic Therapy of Cancer 187<br /> </b><i>K. Eszter Borbas and Dorothée Lahaye</i></p> <p>11.1 Introduction 187</p> <p>11.2 Photosensitizers 196</p> <p>11.3 Outlook 212</p> <p>11.4 Acknowledgement 212</p> <p><b>12 Target-directed Drug Discovery 223<br /> </b><i>Tracey D. Bradshaw</i></p> <p>12.1 Introduction 223</p> <p>12.2 Tyrosine Kinases – Role and Significance in Cancer 226</p> <p>12.3 Targeted Therapy for the Treatment of Non-small Cell Lung Cancer (NSCLC) 226</p> <p>12.4 Targeted Therapy for the Treatment of Chronic Myeloid Leukaemia 229</p> <p>12.5 Targeted Therapy for the Treatment of Breast Cancer 230</p> <p>12.6 Angiogenesis 231</p> <p>12.7 Targeting Cell Cycling 235</p> <p>12.8 Targeting Apoptosis 237</p> <p>12.9 Targeting mTOR 237</p> <p>12.10 The Future of Molecularly Targeted Therapy 238</p> <p><b>13 Tumour Hypoxia: Malignant Mediator 245<br /> </b><i>Jill L. O’Donnell, Aoife M. Shannon, David Bouchier-Hayes</i></p> <p>13.1 Introduction 245</p> <p>13.2 Hypoxia Inducible Factor-1 and Hypoxia 246</p> <p>13.3 HIF-1α Post-translational Changes 247</p> <p>13.4 How Genetics Can Modify HIF 248</p> <p>13.5 How Tumours Overcome Hypoxia with HIF- 1 249</p> <p>13.6 HIF-1 Therapeutics 252</p> <p>13.7 Conclusion 255</p> <p><b>14 Resistance to Chemotherapy Drugs 263<br /> </b><i>Robert O’Connor and Laura Breen</i></p> <p>14.1 Introduction 263</p> <p>14.2 What are the Factors Limiting the Efficacy of Cancer Chemotherapy Treatment? 263</p> <p>14.3 A Classification of the Important Chemotherapy Resistance Mechanisms 265</p> <p>14.4 Illustrative Mechanisms of Pharmacokinetic Resistance 267</p> <p>14.5 Illustrative Mechanisms of Pharmacodynamic Resistance 273</p> <p>14.6 Conclusion 277</p> <p><b>15 Cancer Immunotherapy 283<br /> </b><i>Maria Belimezi</i></p> <p>15.1 The Molecular Basis of Cancer Immunotherapy and Gene Immunotherapy of Cancer 283</p> <p>15.2 Recombinant Monoclonal Antibodies 284</p> <p>15.3 Cell Immunotherapy 292</p> <p>15.4 Cancer Vaccines 296</p> <p><b>16 Gene Therapy 305<br /> </b><i>Maria Belimezi, Teni Boulikas and Michael L. Roberts</i></p> <p>16.1 The Concept of Gene Therapy 305</p> <p>16.2 Steps for Successful Gene Therapy 306</p> <p>16.3 Retroviruses in Cancer Gene Therapy 307</p> <p>16.4 Adenoviruses in Cancer Gene Therapy 308</p> <p>16.5 Gene Therapy of Cancer 310</p> <p>16.6 Cancer Immunotherapy with Cytokine Genes 311</p> <p>16.7 IL-12 in Cancer Immunotherapy 311</p> <p>16.8 Viruses able to Kill Cancer Cells 314</p> <p><b>17 Antisense Agents 317<br /> </b><i>Huma Khan and Sotiris Missailidis</i></p> <p>17.1 Introduction 317</p> <p>17.2 Traditional Antisense Oligonucleotides (ASOs) 318</p> <p>17.3 Ribozymes and DNAzymes 320</p> <p>17.4 RNA Interference and siRNAs 321</p> <p>17.5 Shortcomings of Antisense Therapeutics 322</p> <p>17.6 Antisense Agents in Clinical Trials 324</p> <p>17.7 Concluding Remarks 329</p> <p><b>18 Aptamers as Anticancer Agents 331<br /> </b><i>Vaidehi Makwana, Suzanne Simmons and Sotiris Missailidis</i></p> <p>18.1 Introduction 331</p> <p>18.2 Aptamers in Cancer 332</p> <p>18.3 Final comments 341</p> <p><b>Section III: Other Aspects in Anticancer Therapeutic Development 347</b></p> <p><b>19 Treatment of Cancer in Conjunction with Other Agents 349<br /> </b><i>Gary Robert Smith</i></p> <p>19.1 Introduction 349</p> <p>19.2 Non-steroidal Anti-inflammatory Drugs 353</p> <p>19.3 Angiotensin-converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Blockade 358</p> <p>19.4 Partners in Crime – Dealing with Co-infections 362</p> <p>19.5 Discussion 363</p> <p><b>20 Clinical Trials in Oncology 365<br /> </b><i>Tim Friede, Janet Dunn and Nigel Stallard</i></p> <p>20.1 Clinical Trials 365</p> <p>20.2 Early-Phase (Phase I and Phase II) Clinical Trials in Oncology 368</p> <p>20.3 Confirmatory (Phase III) Trials in Oncology 371</p> <p>20.4 Further Issues in Clinical Trials in Oncology 374</p> <p><b>21 Representative Cancers, Treatment and Market 377<br /> </b><i>Teni Boulikas and Nassos Alevizopoulos</i></p> <p>21.1 Lung Cancer 377</p> <p>21.2 Breast Cancer 378</p> <p>21.3 Prostate Cancer 378</p> <p>21.4 Colorectal Cancer 379</p> <p>21.5 Ovarian Cancer 380</p> <p>21.6 Pancreatic Cancer 380</p> <p>21.7 Gastric Cancer 381</p> <p>21.8 Combination Chemotherapy 382</p> <p>21.9 The Pharmaceutical World of Anticancer Drugs 383</p> <p><b>22 Future Trends in Cancer Therapeutics 387<br /> </b><i>Sotiris Missailidis</i></p> <p>22.1 Introduction 387</p> <p>22.2 Personalized Medicines 388</p> <p>22.3 Delivery Systems 390</p> <p>22.4 Closing Remarks 391</p> <p>Index 393</p>

“This book is very well conceived and well presented.” (<i>Doody's Reviews</i>, June 2009) <p>"This volume provides a comprehensive overview of the wealth of information now available in this important and fast-moving subject." (<i>Anticancer Research</i>, November - December 2008)</p>

<b>Dr Sotiris Missailidis.</b> Department of Chemistry and Analytical Sciences, The Open University, Milton Keynes, UK.

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