Elsevier S & T

Anticancer Drug Development

In stock
No reviews
66.750 KD inc. VAT
License
Table of contents
  • Copyright Pageiv
  • CONTENTSv
  • CONTRIBUTORSxi
  • PREFACExiii
  • Chapter 1. A BRIEF HISTORY OF CANCER CHEMOTHERAPY1
  • Summary1
  • 1. Introduction1
  • 2. Genotoxic (Cytotoxic) Therapy2
  • 3. Growth Control Pathways5
  • 4. Host–Tumor Interactions7
  • 5. Conclusions8
  • References9
  • Chapter 2. NOVEL TARGETS IN THE CELL CYCLE AND CELL CYCLE CHECKPOINTS13
  • Summary13
  • 1. Introduction13
  • 2. Molecular Regulation of Cell Cycle Progression14
  • 3. Molecular Regulation of Cell Cycle Checkpoints15
  • 4. Rationale for Targeting Cyclin-Dependent Kinases and Cell Cycle Checkpoint Pathways17
  • 5. Agents and Strategies for Therapeutic Interference19
  • 6. Conclusions24
  • References25
  • Chapter 3. GROWTH FACTOR AND SIGNAL TRANSDUCTION TARGETS FOR CANCER THERAPY31
  • Summary31
  • 1. Introduction31
  • 2. The ErbB Family of Receptor Tyrosine Kinases (RTKs)32
  • 3. The Ras-Raf-MEK-ERK Signaling Pathway34
  • 4. c-Src Kinase, Signal Transduction, Transformation, and Cancer37
  • 5. Akt38
  • 6. Nuclear Hormone Receptors as Targets for Cancer Therapy40
  • 7. Implications for Drug Discovery and Development43
  • References44
  • Chapter 4. CELL DEATH PATHWAYS AS TARGETS FOR ANTICANCER DRUGS55
  • Summary55
  • 1. Introduction56
  • 2. Two Main Pathways for Drug-Induced Apoptosis56
  • 3. Modulation of Drug-Induced Cell Death by Bcl-2 and Related Proteins58
  • 4. The Central Role of Caspases in Drug-Induced Apoptosis61
  • 5. Synergy between Death Receptors and Cytotoxic Drugs64
  • 6. The Rel/NF-kB/IkB Proteins69
  • 7. Conclusion70
  • References70
  • Chapter 5. DRUG RESISTANCE PATHWAYS AS TARGETS77
  • Summary77
  • 1. Introduction77
  • 2. Targeting Drug Transport78
  • 3. Targeting Cellular Stress Responses81
  • 4. Targeting DNA Repair Systems85
  • 5. Conclusions86
  • References86
  • Chapter 6. ROLE OF MATRIX METALLOPROTEINASES AND PLASMINOGEN ACTIVATORS IN CANCER INVASION AND METAS91
  • Summary91
  • 1. Introduction92
  • 2. The Extracellular Matrix92
  • 3. Cancer Invasion and Metastasis92
  • 4. Cell Adhesion in Cancer94
  • 5. Cancer Cell Motility95
  • 6. Inflammatory Response to Cancer95
  • 7. Proteolytic Enzymes Implicated in Cancer Invasion96
  • 8. MMPIs as Novel Anticancer Agents104
  • 9. Sheddases111
  • 10. The uPA System: Proteolytic Control of MMP Activation111
  • References116
  • Chapter 7. TUMOR VASCULATURE AS A TARGET123
  • Summary123
  • 1. Introduction123
  • 2. How to Inhibit Tumor Angiogenesis127
  • 3. Concluding Remarks131
  • References131
  • Chapter 8. GENE-DIRECTED ENZYME PRODRUG THERAPY137
  • Summary137
  • 1. Introduction137
  • 2. Background138
  • 3. Enzyme-Prodrug Systems138
  • 4. Tailored Prodrugs for GDEPT140
  • 5. The Activation Process148
  • 6. Augmenting the Effect149
  • 7. Exploiting the Bystander Effect and Acquired Immunity150
  • 8. Conclusions151
  • References152
  • Chapter 9. TUMOR ANTIGENS AS TARGETS FOR ANTICANCER DRUG DEVELOPMENT157
  • Summary157
  • 1. Introduction157
  • 2. Antigen Targets for Cancer Vaccines158
  • 3. Tumor Antigens as Targets for Antibody-Based Therapeutics164
  • References168
  • Chapter 10. STRUCTURE-BASED DRUG DESIGN AND ITS CONTRIBUTIONS TO CANCER CHEMOTHERAPY171
  • Summary171
  • 1. Introduction171
  • 2. Antimetabolites173
  • 3. Protease Inhibitors176
  • 4. Protein Kinase Inhibitors179
  • 5. Other Targets181
  • 6. Novel Methods in Structure-Based Drug Design182
  • 7. Conclusions and Current Questions183
  • References183
  • Chapter 11. THE CONTRIBUTION OF SYNTHETIC ORGANIC CHEMISTRY TO ANTICANCER DRUG DEVELOPMENT187
  • Summary187
  • 1. Introduction188
  • 2. Early Rationality188
  • 3. The Random Screening Era: Directly from Screen to Clinic188
  • 4. Organic Synthesis Catches Up: Development of National Product Leads189
  • 5. Development of Synthetic Compounds: Structure–Activity Relationships190
  • 6. Immunotoxins: Synthetic Organic Chemistry Applied to Large Molecules191
  • 7. Organic Synthesis in Rational Design: Tumor-Activated Prodrugs of Cytokines191
  • 8. Early Genomics: Inhibitors of Transmembrane Tyrosine Kinases194
  • 9. The Genomics/Proteomics Era: Combinatorial Chemistry195
  • 10. Conclusion198
  • References199
  • Chapter 12. BIOSYNTHETIC PRODUCTS FOR ANTICANCER DRUG DESIGN AND TREATMENT: THE BRYOSTATINS203
  • Summary203
  • 1. Introduction203
  • 2. Background to the Bryostatins204
  • 3. Comprehensive Review of Bryostatin Scientific and Medical Reports205
  • References220
  • Chapter 13. DNA-ENCODED PEPTIDE LIBRARIES AND DRUG DISCOVERY237
  • Summary237
  • 1. Introduction237
  • 2. Methods for DNA-Encoded Peptide Display237
  • 3. Applications for DNA-Encoded Peptide Libraries241
  • 4. Conclusions246
  • References246
  • Chapter 14. MECHANISM-BASED HIGHTHROUGHPUT SCREENING FOR NOVEL ANTICANCER DRUG DISCOVERY249
  • Summary249
  • 1. Importance of Mechanism-Based Targets in Postgenomic Drug Discovery250
  • 2. High-Throughput Screening251
  • 3. Assay Technologies255
  • 4. Assay Performance and Downstream Evaluation of Bits259
  • 5. Compounds for HTS260
  • 6. Examples of Compounds Identified Through Screening Approaches261
  • 7. Future HTS Developments263
  • 8. Concluding Remarks264
  • References264
  • Chapter 15. TUMOR CELL CULTURES IN DRUG DEVELOPMENT269
  • Summary269
  • 1. Introduction269
  • 2. Growth Inhibition Assays270
  • 3. Clonogenic Assays274
  • 4. Three-Dimensional Cell Cultures: Modeling Extravascular Drug Transport275
  • 5. Modeling of in Vivo Activity by in Vitro Assays278
  • 6. Perspective280
  • References280
  • Chapter 16. SCREENING USING ANIMAL SYSTEMS285
  • Summary285
  • 1. Introduction285
  • 2. Choice of in Vivo Systems for Large-Scale Drug Development286
  • 3. Combined in Vitro/in Vivo Testing Procedure Using Human Tumor Xenografts„The Freiburg Experienc289
  • 4. Use of Transgenic Animals in the Search for New Drugs293
  • 5. Screening for Angiogenesis Inhibitors References295
  • References297
  • Chapter 17. RELEVANCE OF PRECLINICAL PHARMACOLOGY AND TOXICOLOGY TO PHASE I TRIAL EXTRAPOLATION TECH301
  • Summary301
  • 1. Introduction302
  • 2. Historical Perspective302
  • 3. Special Toxicity Evaluations303
  • 4. Recent Examples of Drug Development at NCI303
  • 5. Predictability of Nonclinical Animal Data320
  • 6. Conclusions323
  • References323
  • Chapter 18. CLINICAL TRIAL DESIGN: INCORPORATION OF PHARMACOKINETIC, PHARMACODYNAMIC, AND PHARMACOGE329
  • Summary329
  • 1. Introduction330
  • 2. Rationale for Chemotherapy Optimization330
  • 3. Pharmacokinetic–Pharmacodynamic Relationships332
  • 4. Pharmacogenetics335
  • 5. Strategies to Improve Therapeutic Index340
  • 6. Conclusion and Perspectives347
  • References348
  • Chapter 19. TUMOR IMAGING APPLICATIONS IN THE TESTING OF NEW DRUGS353
  • Summary353
  • 1. Introduction353
  • 2. Positron Emission Tomography354
  • 3. PET in New Drug Evaluation355
  • 4. Conclusions365
  • References365
  • Chapter 20. MECHANISTIC APPROACHES TO PHASE I CLINICAL TRIALS371
  • Summary371
  • 1. Introduction371
  • 2. Mechanism-Based Studies of Established Anticancer Agents to Assess Target Inhibition373
  • 3. Mechanistic Trial Perspectives on Anticancer Agents with Novel Mechanisms373
  • 4. Potential of PET Scanning in the Assessment of Pharmacodynamic End Points381
  • 5. Conclusion381
  • References381
  • INDEX385
Book details
  • Vendor Elsevier S & T
  • SKU 9780120726516
  • ISBN-13 9780080490441

Do you have questions about this book?

Ask an expert!

Description eBook delivery & access Reviews
Here in a single source is a complete spectrum of ideas on the development of new anticancer drugs. Containing concise reviews of multidisciplinary fields of research, this book offers a wealth of ideas on current and future molecular targets for drug design, including signal transduction, the cell division cycle, and programmed cell death. Detailed descriptions of sources for new drugs and methods for testing and clinical trial design are also provided.

KEY FEATURES:
* One work that can be consulted for all aspects of anticancer drug development
* Concise reviews of research fields, combined with practical scientific detail, written by internationally respected experts
* A wealth of ideas on current and future molecular targets for drug design, including signal transduction, the cell division cycle, and programmed cell death
* Detailed descriptions of the sources of new anticancer drugs, including combinatorial chemistry, phage display, and natural products
* Discussion of how new drugs can be tested in preclinical systems, including the latest technology of robotic assay systems, cell culture, and experimental animal techniques
* Hundreds of references that allow the reader to access relevant scientific and medical literature
* Clear illustrations, some in color, that provide both understanding of the field and material for teaching