Description
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.- 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
Table of Contents
Contributors PrefaceChapter 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.
