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Genomics in drug discovery and development / Dimitri Semizarov, Eric Blomme. — Oxford : Wiley, 2009. – (63.3162/S471) |
Contents
Contents
Preface
1. Introduction: Genomics and Personalized Medicine
2. Genomics technologies as tools in drug discovery
2.1. Introduction to Genomics Technologies 25
2.2. Gene Expression Microarrays: Technology 27
2.3. Gene Expression Microarrays: Data Analysis 47
2.4. Comparative Genomic Hybridization: Technology 57
2.5. Comparative Genomic Hybridization: Data Analysis 69
2.6. Microarray-Based DNA Methylation Profiling 76
2.7. Microarray-Based MicroRNA Profiling 80
2.8. Technical Issues in Genomics Experiments and Regulatory Submissions of Microarray Data 86
2.9. Conclusion 92
References 93
3. Genomic Biomarkers
3.1. Introduction to Genomic Biomarkers 105
3.2. DNA Biomarkers 109
3.3. RNA Biomarkers 137
3.4. Clinical Validation of Genomic Biomarkers 148
4. Fundamental Principles of Toxicogenomics
4.1. Introduction 167
4.2. Fundamentals of Toxicogenomics 168
4.3. Analysis of Toxicogenomics Data 176
4.4. Practical and Logistic Aspects of Toxicogenomics 191
4.5. Toxicogenomics Reference Databases 199
4.6. Conclusion 208 References 209
5. Toxicogenomics: Applications to In Vivo Toxicology
5.1. The Value of Toxicogenomics in Drug Discovery and Development 219
5.2. Basic Principles of Toxicology in Drug Discovery and Development 221
5.3. Toxicogenomics in Predictive Toxicology 227
5.4. Toxicogenomics in Mechanistic Toxicology 246
5.5. Toxicogenomics and Target-Related Toxicity 265
5.6. Predicting Species-Specific Toxicity 271
5.7. Evaluation of Idiosyncratic Toxicity with Toxicogenomics 273
5.8. Conclusion 277
References 279
6. Toxicogenomics: Applications in In Vitro Systems
6.1. Introductory Remarks on In Vitro Toxicology 293
6.2. Overview of Current Approaches to In Vitro Toxicology 294
6.3. Toxicogenomics in In Vitro Systems: Technical Considerations 300
6.4. Proof-of-Concept Studies using Primary Rat Hepatocytes
6.5. Use of Gene Expression Profiling to Assess Genotoxicity
6.6. Application of Gene Expression Profiling for In Vitro Detection of Phospholipidosis 309
6.7. Toxicogenomics in Assessment of Idiosyncratic Hepatotoxicity 312
3.8. Do Peripheral Blood Mononuclear Cells Represent a Useful Alternative In Vitro Model? 314
6.9. Current and Future Use of In Vitro Toxicogenomics 316
6.10. Conclusions 319
References 321
7. Germ Line Polymorphisms and Drug Response
7.1. Introduction to Germ Line Polymorphisms 329
7.2. Polymorphisms and Drug Response in Oncology 332
7.3. Polymorphisms and Response to Anticoagulants 343
7.4. Polymorphisms in Neuroscience 345
7.5. Polymorphisms and Drug Response in Immunology 347
7.6. Polymorphisms and Response to Antiviral Agents 353
7.7. Gene Copy Number Polymorphisms 357
7.8. Conclusion: Approaches to Identification of Polymorphisms as Predictors of Drug Response 360
References 375
8. Pharmacogenetics of Drug Disposition
8.1. Introduction 385
8.2. Genes and Polymorphisms Affecting Drug Disposition 387
8.3. Genomic Biomarkers for PK Studies 403
8.4. Utility of PG-PK Studies in Early Clinical Trials 405
8.5. Limitations of PG-PK Studies 408
8.6. Genotyping Technologies 408
8.7. Conclusion 409
References 411
9. Overview of Regulatory Developments and Initiatives Related o the Use of Genomic Technologies in Drug Discovery and Development
9.1. Introduction to Recent Regulatory Developments in the Genomic Area 423
9.2. FDA Guidance on Pharmacogenomic Data Submission 428
9.3. Pharmacogenomic Data Submissions: Draft Companion Guidance 434
9.4. Drug-Diagnostic Co-development Concept Paper 436
9.5. Regulations for In Vitro Diagnostic Assays 439
9.6. Biomarker Qualification 442
9.7. Current Initiatives Relevant to Pharmacogenomics 443
9.8. Future Impact of Genomic Data on Drug Development 444
References 447
Index 449
