Genomics in Drug Discovery and Development
1. Auflage November 2008
480 Seiten, Hardcover
Wiley & Sons Ltd
Kurzbeschreibung
Early characterization of toxicity and efficacy would significantly impact the overall productivity of pharmaceutical R&D and reduce drug candidate attrition and failure. By describing the available platforms and weighing their relative advantages and disadvantages, including microarray data analysis, Genomics in Drug Discovery and Development introduces readers to the biomarker, pharmacogenomic, and toxicogenomics toolbox. The authors provide a valuable resource for pharmaceutical discovery scientists, preclinical drug safety department personnel, regulatory personnel, discovery toxicologists, and safety scientists, drug development professionals, and pharmaceutical scientists.
New, effective strategies for early assessment of drug toxicity and efficacy
Genomics in Drug Discovery and Development introduces readers to the biomarker, pharmacogenomic, pharmacogenetic, and toxicogenomic toolboxes, four promising and rapidly growing areas of genomics research that have begun opening the door to personalized medicine solutions. The authors thoroughly review and analyze all relevant technologies and analytical methods necessary for the competent design and execution of biomarker, pharmacogenomic, pharmacogenetic, and toxicogenomic studies. Moreover, by emphasizing the synergies among these areas, they arm pharmaceutical discovery scientists and drug development professionals with state-of-the-art strategies for reducing drug development time and costs, expediting a drug's approval, and improving its life cycle. Academic researchers will find in this book authoritative and integrated coverage of these rapidly developing and popular areas of genomic research.
Readers involved in laboratory, clinical, or modeling studies who are seeking to assess the toxicity and efficacy of drug candidates as early as possible can rely on this book to help guide their experiments. Topics include:
* Weighing the relative advantages and disadvantages of available genomic technology platforms
* Using pharmacogenomics and pharmacogenetics to position drug studies in the context of clinical trials
* Identifying and validating biomarkers
* Predicting and characterizing the toxicity of drugs
* Applying study findings to improve the productivity of drug discovery
Today's pharmaceutical industry is characterized by exponentially rising R&D costs and a steadily decreasing percentage of approved drugs. Pharmaceutical discovery scientists therefore should take advantage of this book's unique integrated coverage of biomarkers, toxicogenomics, and pharmacogenomics in order to make their own discovery efforts as fruitful as possible.
Chapter 1: Introduction: Genomics and Personalized Medicine (Dimitri Semizarov).
1.1. Fundamentals of genomics.
1.2. The concept of personalized medicine.
1.3. Genomics technologies in drug discovery.
1.4. Scope of this book.
References.
Chapter 2: Genomics Technologies as Tools in Drug Discovery (Dimitri Semizarov).
2.1. Introduction to genomics technologies.
2.2. Gene expression microarrays: technology.
2.3. Gene expression microarrays: data analysis.
2.4. Comparative genomic hybridization: technology.
2.5. Comparative genomic hybridization: data analysis.
2.6. Microarray-based DNA methylation profiling.
2.7. Microarray-based microRNA profiling.
2.8. Technical issues in genomics experiments and regulatory submissions of microarray data.
2.9. Conclusion.
References.
Chapter 3: Genomic Biomarkers (Dimitri Semizarov).
3.1. Introduction into genomic biomarkers.
3.2. DNA biomarkers.
3.3. RNA biomarkers.
3.4. Clinical validation of genomic biomarkers.
References.
Chapter 4: Fundamental Principles of Toxicogenomics (Eric Blomme).
4.1. Introduction.
4.2. Fundamentals of toxicogenomics.
4.3. Analysis of toxicogenomics data.
4.4. Practical and logistic aspects of toxicogenomics.
4.5. Toxicogenomics reference databases.
4.6. Conclusion.
References.
Chapter 5: Toxicogenomics: Applications to In Vivo Toxicology (Eric Blomme).
5.1. The value of toxicogenomics in drug discovery and development.
5.2. Basic principles of toxicology in drug discovery and development.
5.3. Toxicogenomics in predictive toxicology.
5.4. Toxicogenomics in mechanistic toxicology.
5.5. Toxicogenomics and target-related toxicity.
5.6. Predicting species-specific toxicity.
5.7. Evaluation of idiosyncratic toxicity with toxicogenomics.
5.8. Conclusion.
References.
Chapter 6: Toxicogenomics: Applications in In Vitro Systems (Eric Blomme).
6.1. Introductory remarks on in vitro toxicology.
6.2. Overview of the current approaches to in vitro toxicology.
6.3. Toxicogenomics in in vitro systems: technical considerations.
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 the in vitro detection of phopholipidosis.
6.7. Toxicogenomics in the assessment of idiosyncratic hepatotoxicity.
6.8. Do peripheral blood mononuclear cells represent a useful alternative in vitro model?
6.9. Current and future use of in vitro toxicogenomics.
6.10. Conclusion.
References.
Chapter 7: Germ Line Polymorphisms and Drug Response (Dimitri Semizarov).
7.1. Introduction into germline polymorphisms.
7.2. Polymorphisms and drug response in oncology.
7.3. Polymorphisms and response to anticoagulants.
7.4. Polymorphisms in neuroscience.
7.5. Polymorphisms and drug response in immunology.
7.6. Polymorphisms and response to antiviral agents.
7.7. Gene copy number polymorphisms.
7.8. Conclusions: approaches to identification of polymorphisms as predictors of drug response.
References.
Chapter 8: Pharmacogenetics of Drug Disposition (Anahita Bhathena).
8.1. Introduction.
8.2. Genes and polymorphisms affecting drug disposition.
8.3. Genomic biomarkers for PK studies.
8.4. Utility of PG--PK studies in early clinical trials.
8.5. Limitations of PG--PK studies.
8.6. Genotyping technologies.
8.7. Conclusion.
References.
Chapter 9: Overview of Regulatory Developments and Initiatives Related to the Use of Genomic Technologies in Drug Discovery and Development (Eric Blomme).
9.1. Introduction into recent regulatory developments in the genomic area.
9.2. FDA guidance on pharmacogenomic data submission.
9.3. Pharmacogenomic data submission: draft companion guidance.
9.4. Drug-diagnostic co-development concept paper.
9.5. Regulations for in vitro diagnostic assays.
9.6. Biomarker qualification.
9.7. Current initiatives relevant to pharmacogenomics.
9.8. Future impact of genomic data on drug development.
References.
Index.
Eric Blomme, DVM, PhD, Diplomate, American College of Veterinary Pathologists, is a Senior Project Leader for Cellular, Molecular, and Exploratory Toxicology in Global Pharmaceutical R&D at Abbott Laboratories. He has extensive drug discovery, toxicology, and screening experience working for Abbott, Pharmacia, Monsanto, Searle, Ohio State University, and Cornell University. Dr. Blomme has written over fifty journal articles and eight book chapters, and is a reviewer for multiple scientific journals in the fields of toxicology and pathology.