Precision Medicine in Clinical Practice

Description

The book provides complete information on the cornerstones of precision medicine through the omics approach. Clinical applications of genomics and precision medicine have progressed from a theoretical wish list to an impactful force in medical practice.Step-by-step descriptions are provided from basics to the future application and its benefit in clinical practice. Precision medicine aims to personalize health care by tailoring decisions and treatments to each individual in every possible way. Precision medicine includes pharmacogenomics. Essential information is provided on the role of precision medicine and pharmacogenomics in the clinical practice of cancer, cardiovascular disease, diabetes, psychiatric disease, and also the importance for healthcare professionals. This book will assist the practitioners how to integrate precision medicine and pharmacogenomics data into their clinical practice. It is hoped that physicians, pharmacists, and scientists with basic scientific knowledge of precision medicine will findthis book useful. Acknowledgments Contents 1: Principles of Precision Medicine 1.1 An Introduction to Precision Medicine in Clinical Practice 1.2 Definition of Precision Medicine 1.3 Pharmacogenomics 1.4 Precision Medicine in Clinical Practice 1.4.1 The Effectiveness of Care 1.4.2 Preventive Medicine 1.4.3 Cost-Effectiveness 1.4.4 New Taxonomy 1.4.5 Population Healthcare 1.5 Precision Medicine and Evidence-Based Medicine 1.6 Genomics Precision Medicine 1.7 “Omics” and Precision Medicine 1.8 Personalized Medicine, Artificial Intelligence, and Digital Twin References 2: Principles of Pharmacogenomics and Pharmacogenetics 2.1 Introduction to Pharmacogenomics and Pharmacogenetics 2.2 Pharmacodynamics and Pharmacokinetics 2.3 Phenoconversion 2.4 Pharmacogenomics Nomenclature 2.5 Genetic Variations 2.6 Pharmacogenomics in Clinical Practice 2.7 Pharmacogenomics in Drug Development 2.8 Pharmacogenomics in Oncology 2.9 Germline Pharmacogenomics Association with Treatment Efficacy and Toxicity 2.9.1 CYP2D6 and Tamoxifen 2.9.2 Fluoropyrimidines and DPYD 2.10 Implementation of Pharmacogenomics in Oncology 2.11 Pharmacogenomics in Psychiatry 2.12 Implementation of Psychopharmacogenomics in Psychiatry 2.13 Pharmacogenomics in Pain Management 2.13.1 CYP2D6 2.13.2 OPRM1 2.14 Pharmacogenomics in Diabetes 2.15 Future Perspective of Pharmacogenetics in Diabetes 2.16 Pharmacogenomics Resources 2.17 Pharmacogenomics Cases in Practice 2.17.1 Case Study 1: Cardiology 2.17.2 Case Study 2: Depression 2.17.3 Case Study 3: Pain and Phenoconversion 2.17.4 Case Study 4: Schizophrenia and Phenoconversion 2.17.5 Case Study 4: Comprehensive Case Study References 3: Precision Medicine in Oncology and Cancer Therapeutics 3.1 Introduction 3.2 Precision Oncology 1.0: New Lenses for an Old Quest 3.3 Precision Oncology 2.0: The Double Helix and the Rise of Biotechnology 3.4 Precision Oncology 3.0: Cancer, a Diseases of the Genome 3.4.1 Next-Generation Biopharmaceutical Products 3.4.2 Multi-targeted Therapy 3.4.3 New Ways of Reprogramming the Immune System 3.4.4 Advances in Adoptive Cell Therapies 3.4.5 Therapeutic Vaccines 3.5 Oncology 4.0: Fighting Cancer from Multiple Fronts in the Fourth Industrial Revolution 3.5.1 Single-Cell Multiomics for Precision Medicine 3.5.2 Network Medicine and AI 3.5.3 Functional Tests and Organoid-Driven Precision Medicine 3.5.4 A New Era of Biomarkers: Genomic Signatures, Composite Biomarkers, Driver-Pathway Biomarkers, Synthetic Biomarkers 3.5.5 Driver Networks as Biomarkers 3.5.6 The Future of Precision Oncology: The Rise of Digital Twins 3.6 Implementing Precision Oncology in Europe 3.6.1 How Do We Make P4 Medicine a Reality in Medical Practice by Involving Patients, Doctors, Members of the Medical Community, and Citizens? References 4: Precision Medicine in Cardiovascular Disease Practice 4.1 Introduction 4.2 Drugs 4.2.1 Warfarin 4.2.2 VKORC1 4.2.3 CYP2C9 4.2.4 CYP4F2 4.2.5 P2Y12 Inhibitors 4.2.6 Statin 4.3 Cardiomyopathies 4.3.1 Hypertrophic Cardiomyopathy (HCM) 4.3.2 Dilated Cardiomyopathy (DCM) 4.3.3 Restrictive Cardiomyopathy (RCM) 4.4 Thoracic Aortic Aneurysm/Aortic Dissection (TAAD) 4.5 Valvopathies 4.5.1 Mitral Valve Replacement 4.6 Arrhythmia 4.6.1 Long QT Syndrome (LQTS) 4.6.2 Brugada Syndrome (BrS) 4.6.3 Short QT Syndrome (SQTS) 4.6.4 Idiopathic Ventricular Fibrillation (IVF) 4.6.5 Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) 4.6.6 Progressive Cardiac Conduction System Disease (PCCD) 4.7 Coronary Artery Disease (CAD) 4.7.1 Genes and Mechanism 4.7.2 Premature CAD 4.7.3 Vascular Inflammation and Remodeling 4.8 Hypertension 4.9 Recognizing Ethical Issues and How to Deal with Them 4.10 Digital Twin “Prospective of Precision Medicine in Cardiology” References 5: Precision Medicine in Endocrinology Practice 5.1 Precision Diabetes Medicine 5.2 Some Lessons from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) Consensus Report for Precision Medicine in Diabetes 5.3 Precision Diagnostics in Diabetes 5.4 Precision Diagnostics in T1D and T2DM 5.5 Precision Therapeutics of Diabetes 5.6 Precision Prevention 5.7 Precision Treatment/Pharmacogenomics 5.8 Precision Medicine in Osteoporosis 5.9 Precision Medicine in Polycystic Ovary Syndrome 5.10 Thyroid Cancer 5.11 Molecular Genetics of Thyroid Cancer 5.12 Precision Medicine for Thyroid Cancer 5.13 Precision Medicine for Obesity 5.14 Obesity Classification 5.15 Omics and Obesity 5.15.1 Genomics 5.15.2 Transcriptomics 5.15.3 Metabolomics 5.15.4 Microbiome 5.15.5 Pharmacogenomics 5.15.6 Nutrigenetics and Nutrigenomics 5.16 Challenges 5.17 Future Perspective of Precision Medicine in Endocrinology References 6: Precision Medicine in Psychiatric Disorders 6.1 Introduction 6.2 A Special Case for Psychiatry 6.2.1 Psychiatric Disorders Are Multigenic, Multifactorial, and Highly Heterogeneous 6.2.2 From Evidence-Based Through Personalized Toward Precision Psychiatry 6.2.3 The Issue of Psychiatric Measurement and Phenotyping: Objective Markers for Subjective Suffering 6.3 Making Sense of the Information in Precision Psychiatry 6.3.1 Big Data Analytics and Machine Learning Toward a Systems Biological Approach in Understanding and Treating Neuropsychiatric Disorders 6.3.2 Modelling and Predicting Disease and Treatment Characteristics in Precision Psychiatry 6.4 Special Aspects in Precision Psychiatry 6.4.1 The Role of the Blood-Brain-Barrier 6.4.2 Longitudinal Perspective and Staging Model of Neuropsychiatric Disorders 6.4.3 Precision Psychotherapy: Predicting the Efficacy of Psychological Treatment and Identifying Patients Who Would Benefit 6.4.4 Focusing on Comorbidities and Environmental Effects in Precision Psychiatry: The Diseasome Approach 6.5 Clinical Application of Precision Psychiatry 6.5.1 The Current State of Precision Psychiatry in Mood Disorders 6.5.2 The Current State of Precision Psychiatry in Schizophrenia 6.6 Challenges, Obstacles, and Limitations in Precision Psychiatry 6.7 Conclusion References 7: Precision Public Health Perspectives 7.1 Population Health Versus Public Health 7.2 Introduction to Public Health (PH) and Personalized Medicine (PM) 7.3 Impact of Personalized Medicine in Public Health 7.4 Direct Impact 7.5 Indirect Impact: Genetic Information on Preventive Applications, Diagnostic Disease, and Targeted Therapies 7.6 Public Involvement in PM 7.7 Personalized Public Health and Equity References 8: DNA Technologies in Precision Medicine and Pharmacogenetics 8.1 Introduction 8.2 NGS Technology Procedures: Its Important Applications and Related Different Databases 8.3 Whole-Genome Sequencing 8.4 Whole-Exome Sequencing 8.5 Clinical Exome Sequencing 8.6 Whole Transcriptome Sequencing 8.7 Targeted Sequencing 8.8 Single-Cell Sequencing 8.9 DNA Microarray 8.10 Conclusion References 9: Precision Medicine Initiatives 9.1 Introduction 9.2 Precision Medicine Initiatives 9.2.1 The Precision Medicine Initiative (PMI) (United States) 9.2.2 Electronic Medical Records and Genomics (eMERGE) 9.2.3 The Clinical Sequencing Evidence-Generating Research (CSER) 9.2.4 Implementing GeNomics in PracTicE (IGNITE) 9.2.5 ALL of Us 9.2.6 100,000 Genomes 9.2.7 France: The Plan for Genomic Medicine (PFMG) and Health Data Hub 9.2.8 Japan: Initiative on Rare and Undiagnosed Diseases 9.2.9 GenomeCanada 9.2.10 World Economic Forum (WEF): Center for the Fourth Industrial Revolution 9.2.11 European Initiatives Dedicated to Personalized Medicine 9.3 Initiatives Related to Pancreatic Pathology 9.3.1 PanCAN (United States) 9.3.2 Enhanced Pancreatic-Cancer Profiling for Individualized Care (EPPIC) (Canada) 9.3.3 The PancREatic Cancer OrganoiDs rEsearch (PRECODE) (Germany) 9.3.4 The Australian Pancreatic Cancer Genome Initiative (APGI) (Australia) 9.4 Initiatives with the Most Focus on Diabetes 9.4.1 Nordic Precision Medicine Initiative (NPMI) (North Europe) 9.4.2 EPMPP, FinnGen, GAPS, deCODE 9.4.3 Saudi Human Genome Project (SHGP) 9.5 Initiatives Related to Alzheimer’s Disease (AD) 9.5.1 The Genetic Frontotemporal dementia Initiative (GENFI) 9.5.2 The Dominantly Inherited Alzheimer Network (DIAN) 9.5.3 Alzheimer Precision Medicine Initiative (APMI) 9.5.4 Dementias Platform United Kingdom (DPUK) 9.5.5 EU Joint Program on Neurodegenerative Disease Research (EU JPND) 9.5.6 European Prevention of Alzheimer’s Dementia (EPAD) 9.5.7 The AETIONOMY Project 9.5.8 The Women’s Brain Project (WBP) References 10: Economic Aspects in Precision Medicine and Pharmacogenomics 10.1 The Importance of Economic Evaluation in the Field of Precision Medicine 10.2 Challenges of EEs in the Field of Precision Medicine 10.2.1 Lack of Consistent Methods for Conducting Economic Evaluations 10.2.1.1 Enrichment Design 10.2.1.2 Randomized All Designs 10.2.1.3 Basket Clinical Trial 10.2.1.4 Umbrella Trials 10.2.2 Measuring the Real Value of Personalized Medicine 10.2.2.1 Willingness to Pay 10.2.2.2 Benefits Beyond the Health-Related Quality of Life Capability Theory Process Utility Personal Utility 10.2.3 Inadequate Available Data 10.2.4 Increasing Complexity of EEs of PMI 10.2.4.1 Study Question 10.2.4.2 Sensitivity/Specificity and Predictive Value of the Test 10.2.4.3 Cascading Decision in EE of PMI References 11: Ethical, Legal and Social Aspects of Precision Medicine 11.1 Ethical, Social, and Legal Aspects of PM: Research and Healthcare Context 11.2 Data Sharing: Clinical Care and Research 11.3 Patient Recruitment 11.4 Informed Consent (IC) 11.5 Pediatric Informed Consent 11.6 Unsolicited or “Incidental” Findings 11.7 Genetic Service and Biobanks 11.8 Institutional Review Boards (IRB) 11.9 The General Data Protection Regulation (GDPR) and Related Definitions 11.10 Reidentification and Pseudonymization 11.11 Blockchain 11.12 Personal Data 11.13 International Transfers of Personal Data: Regulation (EU) 2018/1725 11.14 Equal Access to Personalized Care 11.15 National Strategy or National Plan on Personalized Medicine 11.16 Examples of International Networks Working on Sharing Data 11.17 Intellectual Property of PM 11.18 Health Technology Assessment (HTA) 11.19 Patient Empowerment/Involvement 11.20 Incentives: Consideration 11.21 Direct-to-Consumer Genetic Testing 11.22 Work and Genetic Discrimination 11.23 Notes About Equity 11.24 ELSA Research Versus ELSA on PM Research References 12: Personalized Medicine Literacy 12.1 Introduction 12.2 What Does Being Healthy Mean? The Determinants of Health During the Time 12.2.1 The Determinants of Health and Precision Cardiology 12.2.2 The Determinants of Health and Precision Oncology 12.2.3 The Determinants of Health and Precision Diabetology 12.2.4 COVID-19 Pandemic and the Social and Behavioral Innovations 12.3 The Role of Attitudes and Perceptions Assessment for Influencing Pro-health Behavior of the Citizens: Two Case Studies on Cancer Literacy and Vaccination Literacy 12.3.1 Cancer Literacy in Romania 12.3.1.1 Cancer Burden in Romania 12.3.2 Attitudes, Perceptions, and Behaviors on Cancer: National Survey (2016, 2018, 2020) in the Romanian Population 12.3.2.1 Fatalism 12.3.2.2 Personalized Medicine and Cancer Innovation Awareness 12.3.2.3 Quality of the Cancer Information Campaigns: From One-Size-Fits-All to Personalized Communication 12.3.3 Vaccination Literacy in Romania 12.3.3.1 HPV Vaccination Literacy Two Sides of the Story About HPV Vaccination Efforts in Romania 12.3.3.2 COVID-19 Vaccination Literacy 12.4 Conclusions and Discussions 12.4.1 Future Perspectives on Increasing the Individual Level of Health Literacy by Periodically Assessing Attitudes, Perceptions, and Behaviors, in Synergy with the European Opportunities References 13: Precision Medicine in Infectious Disease 13.1 Addressing Personalized Medicine Approaches on Infectious Diseases: Prevention, Diagnostic, and Treatment 13.2 Rapid Point-of-Care Diagnostics (POC-Ds) and Their Integration to Decision-Making in General Practice 13.3 Bacterial Infections 13.3.1 Climate Change-Related Infectious Disease 13.3.2 Tuberculosis Diseases (TB) 13.4 Viral Diseases: Zika and HIV Diseases 13.4.1 Zika Diseases 13.4.2 Human Immunodeficiency Virus (HIV) 13.5 Innovation Technologies: CRISPR/Cas9 and by CART (Chimeric Antigen Receptor T Cell) 13.5.1 Neglected Infectious Diseases (NIDs) 13.6 Malaria 13.7 Antimicrobial Resistance Diseases 13.8 Personalized Epidemiology 13.9 Vaccination Strategy 13.10 Microbiome 13.11 Coronaviruses 13.11.1 Introduction 13.12 SARS-CoV-2 Genome 13.13 Variations in SARS-CoV-2 Genome 13.14 Genomics of Host Susceptibility to COVID-19 13.15 Proposed Targets of Repurposed and Investigational Therapies for COVID-19 13.16 Precision Medicine and Pharmacogenomics Approach for COVID-19 13.17 Pharmacogenomics Aspect in COVID-19 Treatment Approach 13.17.1 Hydroxychloroquine and Chloroquine 13.18 Remdesivir 13.19 Viral Protease Inhibitors (Lopinavir, Ritonavir, Atazanavir, Oseltamivir) 13.20 Antimicrobial (Azithromycin) 13.21 Corticosteroids 13.22 RNA-Dependent RNA Polymerase 13.23 Conclusion References