Anticancer Drug Development

Anticancer Drug Development, 1st Edition

Anticancer Drug Development, 1st Edition,Bruce Baguley,David Kerr,ISBN9780120726516

Baguley   &   Kerr   

Academic Press




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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


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.


Oncologists, cancer researchers, pharmacologists, molecular biologists, and cell biologists.

Bruce Baguley

Affiliations and Expertise

The University of Auckland, New Zealand

David Kerr

Affiliations and Expertise

University of Oxford, United Kingdom

Anticancer Drug Development, 1st Edition

Contributors Preface Chapter 1 A Brief History of Cancer Chemotherapy Summary 1. Introduction 2. Genotoxic (Cytotoxic) Therapy 3. Growth Control Pathways 4. Host-Tumor Interactions 5. Conclusions References Chapter 2 Novel Targets in the Cell Cycle and Cell Cycle Checkpoints Summary 1. Introduction 2. Molecular Regulation of Cell Cycle Progression 3. Molecular Regulation of Cell Cycle Checkpoints 4. Rationale for Targeting Cyclin-Dependent Kinases and Cell Cycle Checkpoint Pathways 5. Agents and Strategies for Therapeutic Interference 6. Conclusions References Chapter 3 Growth Factor and Signal Transduction Targets for Cancer Therapy Summary 1. Introduction 2. The ErbB Family of Receptor Tyrosine Kinases (RTKs) 3. The Ras-Raf-MEK-ERK Signaling Pathway 4. c-Src Kinase, Signal Transduction, Transformation, and Cancer 5. Akt 6. Nuclear Hormone Receptors as Targets for Cancer Therapy 7. Implications for Drug Discovery and Development References Chapter 4 Cell Death Pathways as Targets for Anticancer Drugs Summary 1. Introduction 2. Two Main Pathways for Drug-Induced Apoptosis 3. Modulation of Drug-Induced Cell Death by Bcl-2 and Related Proteins 4. The Central Role of Caspases in Drug-Induced Apoptosis 5. Synergy between Death Receptors and Cytotoxic Drugs 6. The Rel/NF-kB/IkB Proteins 7. Conclusion References Chapter 5 Drug Resistance Pathways as Targets Summary 1. Introduction 2. Targeting Drug Transport 3. Targeting Cellular Stress Responses 4. Targeting DNA Repair Systems 5. Conclusions References Chapter 6 Role of Matrix Metalloproteinases and Plasminogen Activators in Cancer Invasion and Metastasis: Therapeutic Strategies Summary 1. Introduction 2. The Extracellular Matrix 3. Cancer Invasion and Metastasis 4. Cell Adhesion in Cancer 5. Cancer Cell Motility 6. Inflammatory Response to Cancer 7. Proteolytic Enzymes Implicated in Cancer Invasion 8. MMPIs as Novel Anticancer Agents 9. Sheddases 10. The uPA System: Proteolytic Control of MMP Activation References Chapter 7 Tumor Vasculature as a Target Summary 1. Introduction 2. How to Inhibit Tumor Angiogenesis 3. Concluding Remarks References Chapter 8 Gene-Directed Enzyme Prodrug Therapy Summary 1. Introduction 2. Background 3. Enzyme-Prodrug Systems 4. Tailored Prodrugs for GDEPT 5. The Activation Process 6. Augmenting the Effect 7. Exploiting the Bystander Effect and Acquired Immunity 8. Conclusions References Chapter 9 Tumor Antigens as Targets for Anticancer Drug Development Summary 1. Introduction 2. Antigen Targets for Cancer Vaccines 3. Tumor Antigens as Targets for Antibody-Based Therapeutics References Chapter 10 Structure-Based Drug Design and its Contributions to Cancer Chemotherapy Summary 1. Introduction 2. Antimetabolites 3. Protease Inhibitors 4. Protein Kinase Inhibitors 5. Other Targets 6. Novel Methods in Structure-Based Drug Design 7. Conclusions and Current Questions References Chapter 11 The Contribution of Synthetic Organic Chemistry to Anticancer Drug Development Summary 1. Introduction 2. Early Rationality 3. The Random Screening Era: Directly from Screen to Clinic 4. Organic Synthesis Catches Up: Development of National Product Leads 5. Development of Synthetic Compounds: Structure-Activity Relationships 6. Immunotoxins: Synthetic Organic Chemistry Applied to Large Molecules 7. Organic Synthesis in Rational Design: Tumor-Activated Prodrugs of Cytokines 8. Early Genomics: Inhibitors of Transmembrane Tyrosine Kinases 9. The Genomics/Proteomics Era: Combinatorial Chemistry 10. Conclusion References Chapter 12 Biosynthetic Products for Anticancer Drug Design and Treatment: The Bryostatins Summary 1. Introduction 2. Background to the Bryostatins 3. Comprehensive Review of Bryostatin Scientific and Medical Reports References Chapter 13 DNA-Encoded Peptide Libraries and Drug Discovery Summary 1. Introduction 2. Methods for DNA-Encoded Peptide Display 3. Applications for DNA-Encoded Peptide Libraries 4. Conclusions References Chapter Mechanism-Based Highthroughput Screening for Novel Anticancer Drug Discovery Summary 1. Importance of Mechanism-Based Targets in Postgenomic Drug Discovery 2. High-Throughput Screening 3. Assay Technologies 4. Assay Performance and Downstream Evaluation of Bits 5. Compounds for HTS 6. Examples of Compounds Identified Through Screening Approaches 7. Future HTS Developments 8. Concluding Remarks References Chapter 15 Tumor Cell Cultures in Drug Development Summary 1. Introduction 2. Growth Inhibition Assays 3. Clonogenic Assays 4. Three-Dimensional Cell Cultures: Modeling Extravascular Drug Transport 5. Modeling of in Vivo Activity by in Vitro Assays 6. Perspective References Chapter 16 Screening Using Animal Systems Summary 1. Introduction 2. Choice of in Vivo Systems for Large-Scale Drug Development 3. Combined in Vitro/in Vivo Testing Procedure Using Human Tumor Xenografts-The Freiburg Experience 4. Use of Transgenic Animals in the Search for New Drugs 5. Screening for Angiogenesis Inhibitors References Chapter 17 Relevance of Preclinical Pharmacology and Toxicology to Phase I Trial Extrapolation Techniques: Elevance of Animal Toxicology Summary 1. Introduction 2. Historical Perspective 3. Special Toxicity Evaluations 4. Recent Examples of Drug Development at NCI 5. Predictability of Nonclinical Animal Data 6. Conclusions References Chapter 18 Clinical Trial Design: Incorporation of Pharmacokinetic, Pharmacodynamic, and Pharmacogenetic Principles Summary 1. Introduction 2. Rationale for Chemotherapy Optimization 3. Pharmacokinetic-Pharmacodynamic Relationships 4. Pharmacogenetics 5. Strategies to Improve Therapeutic Index 6. Conclusion and Perspectives References Chapter 19 Tumor Imaging Applications in the Testing of New Drugs Summary 1. Introduction 2. Positron Emission Tomography 3. PET in New Drug Evaluation 4. Conclusions References Chapter 20 Mechanistic Approaches to Phase I Clinical Trials Summary 1. Introduction 2. Mechanism-Based Studies of Established Anticancer Agents to Assess Target Inhibition 3. Mechanistic Trial Perspectives on Anticancer Agents with Novel Mechanisms 4. Potential of PET Scanning in the Assessment of Pharmacodynamic End Points 5. Conclusion References Index

Quotes and reviews

@qu:"..this is a really extensive and comprehensive book on the drug development process. ...There is very little overlap between chapters and all are written by experts in the field. Hundreds of useful references are included for those wanting to go further. ...Very good value...and essential reading for both the scientist and Ph.D. student. Definately one for the library to stock."
@source:—Paul Loadman, University of Bradford, UK for BRITISH JOURNAL OF CANCER (2002)
@qu:"Well-referenced and indexed...this text would be a useful addition to the clinic, research laboratory and institution library."
@source:—P. Parsons, Queensland Institute of Medical Research for CANCER FORUM (2002)
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