| 查看: 633 | 回复: 3 | |||
| 【奖励】 本帖被评价3次，作者lihai0910增加金币 3 个 | |||
| 当前主题已经存档。 | |||
| 当前只显示满足指定条件的回帖，点击这里查看本话题的所有回帖 | |||
[资源]
Novel Anticancer Agents: Strategies for Discovery and Clinical Testing
|
|||
|
Novel Anticancer Agents: Strategies for Discovery and Clinical Testing By Alex A. Adjei, John K. Buolamwini Publisher: Academic Press Number Of Pages: 464 Publication Date: 2005-12-13 ISBN / ASIN: 0120885611 EAN: 9780120885619 -------------------------------------------------------------------------------- Book Description: This book offers pertinent basic science information on strategies used for the rational design and discovery of novel anticancer agents, and, in addition, translational studies involving clinical trial design and execution with these novel, mostly cytostatic agents. This book covers basic science strategies that are being used in drug discovery and preclinical evaluation focused on novel molecular targets, as well as clinical trial methodology including clinical pharmacokinetics and imaging to address issues of efficacy evaluation of the new, relatively non-cytotoxic anticancer agents. At present, there is no book that provides such an integration of basic and clinical studies of novel anticancer agents, covering both drug discovery and translational research extensively. * Addresses the critical issues involved in the development of novel agents for cancer therapy by experts in the field * Presents drug discovery strategies * Discusses regulatory issues surrounding drug development * I l l CONTENTS CONTRIBUTORS XI PREFACE XV STRATEGIES FOR DRUG DISCOVERY A Survey of Novel Molecular Targets for Anticancer Drug Discovery JOHN K. BUOLAMWlNI I. Introduction 1 II. Overview of Growth Factor Induced Mitogenic Signaling III. Protein Kinases and Phosphatases 4 IV. Adapter Proteins 12 V. GTP-Binding Proteins 12 VI. Oncogenic Transcription Factors 13 VII. Apoptosis, Cell Survival, and Life Span Targets 15 VIII. Angiogenesis and Metastasis Molecular Factors 17 IX. Protein Degradation and Chaperoning Targets 19 X. Chromatin Remodeling Factors 19 XI. Conclusion 20 References 20 V VI CONTENTS 2 Microarrays: Small Spots Produce Major Advances in Pharmacogenomics M. NEESW, . KUSNEZOWA, ND C. D. WOODWORTH I. Introduction to Microarrays 38 II. Advantages of DNA Microarrays 44 III. Major DNA Array Formats: Something for Everyone 45 IV. What is the Best Way to Interface with Microarrays? 52 V. Microarrays and Pharmacogenomics: Revolutionizing Discovery of New Drugs and Gene Function 55 VI. What Can Go Wrong in cDNA Microarray Experimentation? 65 VII. Array-Based Proteomics: How to Investigate Protein Complexity 68 VIII. Emerging Microarray Technologies for High-Throughput Proteome Investigation: A Technical Overview 68 IX. Current and Future Applications of Protein Arrays in Drug Discovery 71 X. How to Deal with all that Data 73 XI. The Future is Only Going to Get Better 74 References 76 3 Strategies to Target Chemotherapeutics to Tumors CHARLES E ALBRIGHT AND PEARL S. HUANG I. Background and Rationale 83 II. Antibody-Directed Enzyme Prodrug Technique 84 III. Passive Tumor Targeting 84 IV. Targeting by Binding to Tumor Cell Surface Molecules 85 V. Enzyme-Activated Targeting 85 VI. Summary and Future Directions 90 References 90 4 QSAR and Pharmacophore Mapping Strategies in Novel Anticancer Drug Discovery JAMES J. KAMINSKI I. Introduction 93 II. Pharmacophore Definition III. Pharmacophore Validation IV. Conclusions 104 References 104 5 Applications of Nuclear Magnetic Resonance and Mass Spectrometry t o Anticancer Drug Discovery ROBERT POWERS AND MARSHALL M. SIEGEL I. Introduction 107 II. NMR in Anticancer Drug Discovery 109 III. Mass Spectrometry in Anticancer Drug Discovery 140 IV. MS/NMR Screening Assay V. Conclusions 172 Acknowledgements 172 References 173 162 6 Antisense Strategies for the Development of Novel Cancer Therapeutics RUIWEN ZHANG AND HUI WANG I. Introduction 191 II. Design and Evaluation of Antisence Oligonucleotides III. Conclusion 202 Acknowledgements 203 References 203 193 7 Antibodies and Vaccines as Novel Cancer Therapeutics SVETOMIR N. MARKOVIC AND ESTEBAN CELLS I. Introduction 207 II. Anti-Tumor Antibodies III. Cancer Vaccines 212 IV. Conclusion 218 References 219 207 8 Inhibitors of Apoptosis as Targets for Cancer Therapy M. SAEED SHEIKH AND YING HUANG I. The Inhibitors of Apoptosis II. Concluding Remarks 229 References 230 223 9 Preclinical Testing and Validation of Novel Anticancer Agents LLOYD R. KELLAND I. Introduction 233 II. Target Validation 234 III. A Generic Cascade for Anticancer Drug Discovery 235 IV. High-Throughput Cell-Free Screens for Activity Against the Target 237 V. In Vitro Cell Line Models 238 VI. In Vivo Testing of Novel Compounds 240 VII. Cassette-Dosing 240 VIII. Pharmaceutical Considerations 241 IX. High-Throughput In Vivo Anti-Tumor Testing: The Hollow Fiber Assay 241 X. Human Tumor Xenografts 242 XI. Orthotopic, Transgenic, and Other Animal Models 243 V I I I CONTENTS XII. Pharmacodynamics 244 XIII. Summary 245 Acknowledgements 245 References 245 METHODS FOR CLINICAL TESTING OF NOVEL AGENTS I 0 Surrogate End Points and Biomarkers for Early Trials of Novel Anticancer Agents ALEX A. ADJEI I. Introduction 249 II. What are Targeted Agents? 250 III. Surrogate Markers or Biomarkers? 250 IV. Biomarkers as Indicators of Drug Effect In Vivo 252 V. Biomarkers as Predictive Factors 252 VI. Biomarkers as Prognostic Factors 253 VII. Technical Issues in the Evaluation of Drug Effects In Vivo VIII. Lessons for the Future 261 Acknowledgements 261 References 261 II Regulatory Considerations in Clinical Trials of Novel Anticancer Drugs GRANT WILLIAMS AND RICHARD PAZDUR 254 I. Introduction 263 II. Overview of Cancer Drug Regulation 264 III. Regulatory Considerations in Early Cancer Drug Development IV. Regulatory Considerations in Late Drug Development 271 V. Conclusion 283 Acknowledgements 283 References 283 12 Improving the Efficacy and Safety of Anticancer Agents--The Role of Pharmacogenetics MARGARET-MARY AMEYAW AND HOWARD L. MCLEOD 267 I. Introduction 286 II. Thiopurine Methyltransferase 286 III. DPD 288 IV. Thymidylate Synthase 289 V. ABC Family of Drug Transporters 291 VI. UDP-Glucuronosyltransferase IAI Pharmacogenetics and Irinotecan VII. MTHFR Reductase Pharmacogenetics 293 VIII. Cytochrome P4503A Pharmacogenetics 293 IX. Conclusion 293 Acknowledgements 294 References 294 292 13 Imaging of Pharmacodynamic End Points in Clinical Trials ERIC O. ABOAGYE, A. R. PADHANI, AND PATRICIA M. PRICE I. Introduction 300 II. PET 300 III. Evaluation of Cancer Therapeutics with PET 302 IV. MRI Assessment of Microvessel Function 311 V. Conclusions 328 References 328 14 Devising Proof-of-Concept Strategies in Oncology Clinical Trials PAUL S. WISSEL I. Introduction 337 II. Proof-of-Concept 338 III. Elements of "The Concept" 339 IV. Application of Surrogate End Points in Proof-of-Concept Decision Making 343 V. Selected Statistical Considerations in Proof-of-Concept Studies 349 VI. Pharmacodynamic Proof-of-Concept End Points 352 VII. Pharmacokinetic Proof-of-Concept End Points 356 VIII. Proceeding From Proof-of-Concept Directly to Phase III 359 IX. Guidelines and Summary 360 Acknowledgements 361 References 361 1 5 Clinical Trial Designs for Cytostatic Agents and Agents Directed at Novel Molecular Targets EDWARD L. KORN, LARRY V. RUBINSTEIN, SALLY A. HUNSBERGER, ]AMES M. PLUDA, ELIZABETH EISENHAUER, AND SUSAN G. ARBUCK I. Introduction 366 II. Phase I Dose-Finding Trials 366 III. Preliminary Efficacy Trials 372 IV. Definitive Randomized Efficacy Trials V. Conclusions 377 References 377 376 X CONTENTS 16 Cancer Gene Therapy Clinical Trials: From the Bench to the Clinic EVANTHIA GALANIS I. Regulatory Requirements and Good Manufacturing Practices for Gene Transfer Products 381 II. Preclinical Development of Gene Therapy Vectors/Toxicology Testing 382 III. Federal and Institutional Approval Processes for Clinical Gene Therapy Trials 383 IV. Gene Therapy Clinical Trial Design 384 V. Correlative End Points 386 References 389 17 Molecular Targets for Radiosensitization ROGER OVE AND JAMES A. BONNER I. Introduction 391 II. Growth Factor Receptors 394 III. Ras 399 IV. Modulation of p53 401 V. DNA Damage Recognition and Repair VI. Other Promising Approaches 405 VII. Conclusions 407 VIII. Addendum 407 Addendum References 409 References 409 18 Patient Accrual to Clinical Trials SUSAN QUELLA 402 I. Introduction 415 II. Setting Up the Environment References 425 Index 427 http://www.91files.com/?ZSWLRFR3BEJOJIBSWJ4C |
回复此楼» 收录本帖的淘帖专辑推荐
 药物化学 |
» 猜你喜欢
2025年遐想
已经有4人回复
-
投稿Elsevier的杂志（返修），总是在选择OA和subscription界面被踢皮球
已经有8人回复
-
自然科学基金委宣布启动申请书“瘦身提质”行动
已经有4人回复
-
求个博导看看
已经有18人回复