Pharmacogenomics

Pharmacogenomics: Challenges and Opportunities in Therapeutic Implementation includes discussions and viewpoints from the academic, regulatory, pharmaceutical, clinical, socio-ethical and economic perspectives. Each chapter presents an overview of the potential or opportunity within the areas discussed and also outlines foreseeable challenges and limitations in moving pharmacogenomics into drug development and direct therapeutic applications. This edited book contains review questions for a more in-depth analysis of the implications of pharmacogenomics and discussion points to generate ideas on best to move the field forward. Clinical pearls and case studies are used to illustrate real-life experiences and both successful and unsuccessful applications. Tables, figures, and annotations are included throughout the book to facilitate understanding and further reference.

• Multi-contributed book and chapters are written by contributors who are experts in their field
• Provides perspectives from those involved in all aspects of pharmacogenomics—including academic, regulatory, economic, industry and medical—to illustrate how all of the pieces fit together and where the challenges may be
• Includes case studies of both successful and unsuccessful applications so readers can consider the potential and challenges in moving the science into drug development and direct therapeutic applications
• Chapters contain discussion questions and clinical pearls and enable readers to reflect on how to move pharmacogenomics forward and apply these observations and useful tips to their own work and research

This book is intended for scientists and clinicians interested in pharmacogenomics implementation in academic, research, medical and pharmaceutical industry settings. Relevant fields include pharmacology, pharmaceutical sciences, genetics, molecular biology and medicine. This book may also be used as a recommended textbook for pharmacy students and graduate-level students in health and pharmaceutical science programs. 

Dedication

List of Contributors

Preface

Chapter 1. Principles of Pharmacogenomics: Pharmacokinetic, Pharmacodynamic, and Clinical Implications

Objectives

Introduction

Cytochrome P-450 Enzymes

Non-CYP-450 Drug Metabolizing Enzymes

Polymorphisms in Drug Transporter Genes

Drug Target Genes

Conclusion

Questions for Discussion

References

Chapter 2. Translating Pharmacogenomic Research to Therapeutic Potentials

Objectives

Introduction

Implementation of Biomarkers in Clinical Practice

Incorporating Pharmacogenomics into Drug Development

Conclusion

Questions for Discussion

References

Chapter 3. Governmental and Academic Efforts to Advance the Field of Pharmacogenomics

Objectives

Introduction

The Role of the National Institutes of Health

The Role of the Food and Drug Administration and Other International Government Agencies

Activities of Non-U.S. Agencies

Conclusion

Questions for Discussion

References

Chapter 4. Pharmacogenomics in Cancer Therapeutics

Objectives

Introduction

Role of Oncology Biomarkers

Concepts in Targeted Cancer Therapy

Oncology in the Postgenomic Era

Challenges in Drug Development and Cancer Trials

Seeking Pharmacogenomic Value

Questions for Discussion

References

Chapter 4A. A Look to the Future: Cancer Epigenetics

Learning Objectives

Introduction

Histone Modification

DNA Methylation

Noncoding RNA (ncRNA)

Conclusion

Questions for Discussion

References

Chapter 5. Pharmacogenetics in Cardiovascular Diseases

Objectives

Introduction

Pharmacogenomics of Antiplatelet Agents

Warfarin Pharmacogenomics

Other Genetic Contributions to Warfarin Dose Variability and Response

Trials and Tribulations of Pharmacogenomics of Agents Used to Treat Dyslipidemia

Pharmacogenomic Potential in Heart Failure

Genetic Influences of Drug-Induced Arrhythmia

Conclusion

Discussion Points

Discussion Questions

References

Chapter 5A. A Look to the Future: Cardiovascular Pharmacoepigenetics

Learning objectives

Introduction

Opportunities

Challenges

Conclusion

Questions for Discussion

References

Chapter 6. Pharmacogenomics in Psychiatric Disorders

Objectives

Introduction

Polymorphisms in Proteins that Affect Drug Concentrations

Polymorphisms in Proteins that Mediate Drug Response

Application of Pharmacogenomics in Psychiatry

Conclusion

Questions for Discussion

References

Chapter 6A. A Look to the Future: Epigenetics in Psychiatric Disorders and Treatment

Objectives

Nature and Nurture Both Contribute to the Etiologies of Psychiatric Disorders

Epigenetic Processes Are Likely to Contribute to the Biochemical Basis of “Nurture”

Epigenetic Dysfunction Has Been Linked to Psychiatric and Neurological Disorders

Epigenetic Processes May Be Critical to Treatment Response in Psychiatric Disorders

Epigenetic Variation of Genes Regulating Pharmacokinetic Processes Is Likely to Influence Treatment Response

Epigenetic Modifications of Drug Transporters

Epigenetics and Adverse Drug Reactions

Limitations of Epigenetic Biomarkers in Psychiatry

Conclusion

Questions for Discussion

References

Chapter 7. The Role of Pharmacogenomics in Diabetes, HIV Infection, and Pain Management

Objectives

Introduction

Diabetes Overview

Type 2 Diabetes Pharmacogenomics

Challenges and Opportunities of Pharmacogenomics in Diabetes

Pharmacogenomics and HIV

Pharmacogenomics and Pain Control

Conclusion

Questions for Discussion

References

Chapter 8. Molecular Approaches, Models, and Techniques in Pharmacogenomic Research and Development

Objectives

Introduction

Human Genetic Variation

Strategies in Pharmacogenomic Research and Development

Bioinformatic Resources for Pharmacogenomic Research and Development

Conclusion and Outlook

Acknowledgement

Questions for Discussion

References

Chapter 8A. Modeling the Pharmacogenetic Architecture of Drug Response

Objectives

Introduction

Genetic Mapping

Functional Genome-Wide Association Study

Discussion

Questions for Discussion

Acknowledgements

References

Chapter 9. Study Designs in Clinical Pharmacogenetic and Pharmacogenomic Research

Objectives

Introduction

Clinical Study Designs to Discover and Confirm the Impact of Human Pharmacogenetic Variation

Conclusion and Perspectives

Questions for Discussion

References

Chapter 9A. Incorporating Pharmacogenomics in Drug Development: A Perspective from Industry

Objectives

Introduction

Pharmacogenomics in Different Phases of Drug Development

Drug Target Screening and Identification

Preclinical Animal Toxicology Studies

Phase I Studies

Phase II and III Studies

Phase IV Studies

Challenges in Applying Pharmacogenomics in Drug Development

Future Perspective

Discussion Questions

References

Chapter 10. The Importance of Ethnicity Definitions and Pharmacogenomics in Ethnobridging

Objectives

Introduction

Ethnicity

Ethnic Factors Affecting Drug Response

Acceptability of Foreign Clinical Data

Conclusion

Discussion Questions

References

Chapter 11. Beyond ELSIs: Where to from Here? From “Regulating” to Anticipating and Shaping the Innovation Trajectory in Personalized Medicine

Objectives

Pharmacogenetics: An Old Science that Stood the Test of Time

Pharmacogenomics: An Old Science Becomes Large-Scale and Global

Rethinking Bioethics in the Twenty-First Century

Beyond Classic ELSIs

An Invitation to Reflexive and Global Bioethics

Conclusion

Discussion Questions

Acknowledgments

References

Chapter 12. Pharmacoeconomics of Pharmacogenetics within the Context of General Health Technology Assessments

Objectives

Introduction

Criteria for Decision Making

Pharmacoeconomics/Health Economics within the HTA Context

Process

Conclusion

Questions for Discussion

References

Appendix: Case Study in the Netherlands

Appendix 1 References

Chapter 13. Integrating Genomics into Pharmacy Education and Practice: Pharmacogenomics Is Not Enough

Objectives

Introduction: The Case for Genomics

Technology as the Driver of Genomic Science

The Critical Gap in Pharmacy Education

Educational Competencies

Conclusion

Questions for Discussion

References

Color Plates

Index