Jain Textbook of Personalized Medicine

1. Auflage 2009
ISBN: 978-1-4419-0769-1
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 430 Seiten

Personalized medicine, which simply means selection of treatment best suited for an individual, involves integration and translation of several new technologies in clinical care of patients. The scope is much broader than indicated by the term genomic medicine because many non-genomic factors are taken into consideration in developing personalized medicine. Basic technologies for personalized medicine, of which molecular diagnostics has the biggest share, are mentioned briefly and appropriate references are given for further information. Commercial aspects are discussed briefly in a chapter and detailed analysis of markets and companies involved in personalized medicine is presented in a special report on this topic. There is increasing interest in personalized medicine. Considerable advances have taken place in molecular biology and biotechnology to make personalized medicine a viable option, but some misconceptions still exist, both in the academic and commercial sectors. There is lack of a suitable source of information that provides both the fundamentals as well as applications of personalized medicine. As the latest version of the first monograph on personalized medicine published in 1998, this volume, Textbook of Personalized Medicine, summarizes the author's efforts during the past decade, as well as reviews selected studies done during this period in a readable format for the physicians and scientists. It is hoped that physicians, pharmacists, scientists and interested lay readers with basic scientific knowledge will find this book useful.

Professor K. K. Jain is trained in neurosurgery with specialist qualifications. He worked for 25 years in various academic positions and private practice worldwide mostly in Canada and the US. His clinical research interests during these years were use of lasers for microneurosurgery and hyperbaric oxygen. He has been involved in biotechnology since 1989, when he moved to Basel, Switzerland. He was elected a fellow of the Faculty of Pharmaceutical Medicine of the Royal Colleges of UK in 2000. He is the author of over 405 publications including 15 books and 48 special reports. Important books are Textbook of Gene Therapy, Textbook of Hyperbaric Medicine and Handbook of Nanomedicine. He is a member of editorial board of several journals and senior associate editor of MedLink Neurology (San Diego, California), a continuing education program for neurologists. Prof. Jain has been interested in integrating various biotechnologies to develop personalized medicine since 1997. He wrote the first report on personalized medicine, which was published in 1998 by Decision Resources Inc. The report titled Personalized Medicine: scientific and commercial aspects is continuously updated and published at Jain PharmaBiotech, Basel. He lectures and conducts workshops worldwide.

Autoren/Hrsg.

Jain, Kewal K.

Inhaltsverzeichnis

1;FM1.pdf;1
2;1.pdf;24
2.1;Chapter 1;24
2.1.1;Basics of Personalized Medicine;24
2.1.1.1;Definition of Personalized Medicine;24
2.1.1.2;History of Medical Concepts Relevant to Personalized Medicine;26
2.1.1.3;Molecular Biological Basis of Personalized Medicine;28
2.1.1.3.1;The Human Genome;29
2.1.1.3.2;Chromosomes;29
2.1.1.3.3;Genes;30
2.1.1.3.3.1;The Genetic Code;30
2.1.1.3.3.2;Gene Expression;31
2.1.1.3.3.3;DNA Sequences and Structure;31
2.1.1.3.3.4;Single Nucleotide Polymorphisms;32
2.1.1.3.3.5;Genotype and Haplotypes;32
2.1.1.3.4;Genetic Variations in the Human Genome;32
2.1.1.3.4.1;Insertions and Deletions in the Human Genome;33
2.1.1.3.4.2;Large Scale Variation in Human Genome;34
2.1.1.3.4.3;Variation in Copy Number in the Human Genome;34
2.1.1.3.4.4;Structural Variants in the Human Genome;35
2.1.1.3.4.5;Mapping and Sequencing of Structural Variants from Human Genomes;36
2.1.1.3.4.6;1,000 Genomes Project;37
2.1.1.3.4.7;Human Variome Project;38
2.1.1.4;Basics Technologies for Developing Personalized Medicine;38
2.1.1.4.1;Definitions of Technologies Relevant to Personalized Medicine;38
2.1.1.4.2;Problems with the ICH Definitions of Pharmacogenomics and Pharmacogenetics;39
2.1.1.4.3;Relationship of Various Technologies to Personalized Medicine;39
2.1.1.5;Conventional Medicine vs. Personalized Medicine;40
2.1.1.6;Genetic Basis of Personalized Medicine;41
2.1.1.6.1;Genetic Medicine;41
2.1.1.6.2;Human Disease and Genes;41
2.1.1.6.3;Genetic and Environmental Interactions in Etiology of Human Diseases;42
2.1.1.6.4;Mass Analysis of DNA from Whole Populations;42
2.1.1.6.5;Role of Genetics in Development of Personalized Medicines;43
2.1.1.6.5.1;Genetic Databases;43
2.1.1.6.5.2;Genetic Epidemiology;44
2.1.1.6.5.3;Limitations of Medical Genetics and Future Prospects;45
2.1.1.6.5.4;Genetics vs. Epigenetics;45
2.1.1.7;Role of Systems Biology in Personalized Medicine;45
2.1.1.7.1;Systems Pharmacology;47
2.1.1.7.2;Systems Medicine;47
2.1.1.8;A Personalized Approach to Environmental Factors in Disease;48
2.1.1.9;Reclassification of Diseases;49
2.1.1.10;Summary;50
3;2.pdf;51
3.1;Chapter 2;51
3.1.1;Molecular Diagnostics as Basis of Personalized Medicine;51
3.1.1.1;Introduction;51
3.1.1.2;Molecular Diagnostic Technologies;51
3.1.1.3;DNA Sequencing;52
3.1.1.4;Biochips and Microarrays;52
3.1.1.4.1;DNA Biochip Technology for Developing Personalized Medicine;52
3.1.1.4.2;Role of Protein Biochips in Personalized Medicine;56
3.1.1.5;Cytogenetics;57
3.1.1.5.1;Molecular Cytogenetics as Basis for Personalized Medicine;57
3.1.1.5.2;Cytomics as a Basis for Personalized Medicine;58
3.1.1.6;SNP Genotyping;59
3.1.1.6.1;Technologies for SNP Analysis;59
3.1.1.6.2;Applications of SNPs Relevant to Personalized Medicine;59
3.1.1.6.3;Concluding Remarks on SNP Genotyping;61
3.1.1.7;Haplotyping;62
3.1.1.7.1;HapMap Project;63
3.1.1.7.2;Predicting Drug Response with HapMap;64
3.1.1.8;Nanodiagnostics for Personalized Medicine;64
3.1.1.8.1;Cantilevers for Personalized Medical Diagnostics;65
3.1.1.8.2;Nanopore-Based Technology for Single Molecule Identification;66
3.1.1.9;Application of Proteomics in Molecular Diagnosis;66
3.1.1.9.1;Comparison of Proteomic and Genomic Approaches in Personalized Medicine;66
3.1.1.10;Gene Expression Profiling;67
3.1.1.10.1;DNA Microarrays for Gene Expression Studies;68
3.1.1.10.2;Analysis of Single-Cell Gene Expression;69
3.1.1.10.3;Gene Expression Profiling Based on Alternative RNA Splicing;69
3.1.1.11;Molecular Imaging and Personalized Medicine;70
3.1.1.11.1;Monitoring In Vivo Gene Expression by Molecular Imaging;71
3.1.1.12;Glycomics-Based Diagnostics;71
3.1.1.13;Combination of Diagnostics and Therapeutics;72
3.1.1.14;Point-of-Care Diagnosis;72
3.1.1.14.1;Point-of-Care Diagnosis of Infections;74
3.1.1.14.2;Advantages vs. Disadvantages of Point-of-Care Diagnosis;74
3.1.1.14.3;Future Prospects of Point-of-Care Diagnosis;75
3.1.1.15;Genetic Testing for Disease Predisposition;75
3.1.1.15.1;Personal Genetic Service;76
3.1.1.16;Role of Diagnostics in Integrated Healthcare;76
3.1.1.16.1;Concept of Integrated Healthcare;76
3.1.1.16.2;Components of Integrated Healthcare;77
3.1.1.16.2.1;Screening;77
3.1.1.16.2.2;Disease Prediction;77
3.1.1.16.2.3;Early Diagnosis;77
3.1.1.16.2.4;Prevention;78
3.1.1.16.2.5;Therapy Based on Molecular Diagnosis;78
3.1.1.16.2.6;Monitoring of Therapy;78
3.1.1.16.3;Advantages and Limitations of Integrated Healthcare;78
3.1.1.17;Future of Molecular Diagnostics in Personalized Medicine;79
3.1.1.18;Summary;79
4;3.pdf;81
4.1;Chapter 3;81
4.1.1;Role of Biomarkers in Personalized Medicine;81
4.1.1.1;Introduction;81
4.1.1.2;Technologies for Discovery of Biomarkers;82
4.1.1.2.1;Systems Biology Approach to Biomarker Identification;82
4.1.1.2.2;Epigenomic Technologies;82
4.1.1.2.2.1;Discovery of Methylation Biomarkers;84
4.1.1.2.3;Proteomic Strategies for Biomarker Identification;84
4.1.1.2.3.1;Proteomic Technologies for Detection of Biomarkers in Body Fluids;85
4.1.1.3;Biomarkers for Diagnostics;85
4.1.1.4;Biomarkers for Drug Development;86
4.1.1.4.1;Use of Biomarkers for Developing MAb Therapy in Oncology;86
4.1.1.5;Biobanking, Biomarkers and Personalized Medicine;87
4.1.1.6;Expression Signatures as Diagnostic/Prognostic Tools;88
4.1.1.7;Biomarkers for Monitoring Response to Therapy;88
4.1.1.8;Drug Rescue by Biomarker-Based Personalized Medicine;89
4.1.1.9;Future Role of Biomarkers in Personalized Medicine;90
4.1.1.10;Summary;90
5;4.pdf;91
5.1;Chapter 4;91
5.1.1;Pharmacogenetics;91
5.1.1.1;Basics of Pharmacogenetics;91
5.1.1.2;Role of Molecular Diagnostics in Pharmacogenetics;92
5.1.1.3;Role of Pharmacogenetics in Pharmaceutical Industry;93
5.1.1.3.1;Study of the Drug Metabolism and Pharmacological Effects;93
5.1.1.3.2;Causes of Variations in Drug Metabolism;94
5.1.1.3.3;Enzymes Relevant to Drug Metabolism;94
5.1.1.3.4;Pharmacogenetics of Phase I Metabolism;95
5.1.1.3.4.1;Cyp450;95
5.1.1.3.4.2;P450 CYP 2D6 Inhibition by Selective Serotonin Reuptake Inhibitors (SSRIs);97
5.1.1.3.4.3;Cytochrome P450 Polymorphisms and Response to Clopidogrel;98
5.1.1.3.4.4;Lansoprazole and Cytochrome P450;98
5.1.1.3.4.5;Glucose-6-Phosphate Dehydrogenase;99
5.1.1.3.5;Pharmacogenetics of Phase II Metabolism;100
5.1.1.3.6;N-Acetyltransferase;100
5.1.1.3.6.1;Uridine Diphosphate-Glucuronosyltransferase;101
5.1.1.3.7;Measurement of CYP Isoforms;101
5.1.1.3.8;Polymorphism of Drug Transporters;102
5.1.1.3.9;Genetic Variation in Drug Targets;103
5.1.1.3.9.1;Polymorphisms of Kinase Genes;104
5.1.1.3.10;Effect of Genetic Polymorphisms on Response of Disease to Drugs;104
5.1.1.3.11;Ethnic Differences in Drug Metabolism;105
5.1.1.3.12;Gender Differences in Pharmacogenetics;105
5.1.1.3.13;Role of Pharmacogenetics in Drug Safety;106
5.1.1.3.13.1;Adverse Drug Reactions;106
5.1.1.3.13.2;ADRs in Children;106
5.1.1.3.13.3;Genetically Determined ADRs;107
5.1.1.3.13.4;ADRs of Chemotherapy;108
5.1.1.3.13.5;Malignant Hyperthermia;109
5.1.1.3.13.6;Pharmacogenetics of Clozapine-Induced Agranulocytosis;109
5.1.1.3.13.7;Role of Pharmacogenetics in Warfarin Therapy;110
5.1.1.3.13.8;Role of Pharmacogenetics in Carbamazepine Therapy;111
5.1.1.3.13.9;Role of Pharmacogenetics in Statin Therapy;111
5.1.1.3.13.10;FDA Consortium for Genetic Biomarkers of Serious Adverse Events;112
5.1.1.3.14;Therapeutic Drug Monitoring, Phenotyping, and Genotyping;113
5.1.1.3.14.1;Therapeutic Drug Monitoring;113
5.1.1.3.14.2;Phenotyping;113
5.1.1.3.14.3;Genotyping;115
5.1.1.3.14.4;Genotyping vs. Phenotyping;115
5.1.1.3.15;Phenomics;116
5.1.1.3.15.1;Limitations of Genotype-Phenotype Association Studies;117
5.1.1.3.16;Molecular Toxicology in Relation to Personalized Medicines;117
5.1.1.3.16.1;Toxicogenomics;117
5.1.1.3.16.2;Gene Expression Studies;118
5.1.1.3.16.3;Genomics and the Prediction of Xenobiotic Toxicity;119
5.1.1.3.17;Pharmacogenetics in Clinical Trials;119
5.1.1.4;Clinical Implications of Pharmacogenetics;120
5.1.1.4.1;Application of CYP450 Genotyping in Clinical Practice;120
5.1.1.4.1.1;Genotype-Based Drug Dose Adjustment;120
5.1.1.4.2;Examples of use of Pharmacogenetics in Clinical Pharmacology;121
5.1.1.4.3;Linking Pharmacogenetics with Pharmacovigilance;122
5.1.1.4.3.1;Genetic Susceptibility to ADRs;122
5.1.1.4.3.2;Linking Genetic Testing to Postmarketing ADR Surveillance;122
5.1.1.4.4;Recommendations for the Clinical Use of Pharmacogenetics;123
5.1.1.5;Limitations of Pharmacogenetics;123
5.1.1.6;Future Role of Pharmacogenetics in Personalized Medicine;124
5.1.1.7;Summary;124
6;5.pdf;126
6.1;Chapter 5;126
6.1.1;Pharmacogenomics;126
6.1.1.1;Introduction;126
6.1.1.2;Basics of Pharmacogenomics;126
6.1.1.3;Pharmacogenomics and Drug Discovery;128
6.1.1.3.1;Preclinical Prediction of Drug Efficacy;129
6.1.1.4;Pharmacogenomics and Clinical Trials;130
6.1.1.4.1;Impact of Genetic Profiling on Clinical Studies;130
6.1.1.4.2;Limitations of the Pharmacogenomic-Based Clinical Trials;132
6.1.1.5;Pharmacogenomic Aspects of Major Therapeutic Areas;133
6.1.1.5.1;Oncogenomics;133
6.1.1.5.2;Oncogenes;133
6.1.1.5.3;Tumor Suppressor Genes;134
6.1.1.5.4;Cardiogenomics;134
6.1.1.5.5;Neurogenomics;138
6.1.1.5.6;Pharmacogenomics of AD;138
6.1.1.5.7;Pharmacogenomics of Depression;139
6.1.1.5.8;Pharmacogenomics of Schizophrenia;139
6.1.1.6;Summary;140
7;6.pdf;141
7.1;Chapter 6;141
7.1.1;Role of Pharmacoproteomics;141
7.1.1.1;Basics of Proteomics;141
7.1.1.2;Proteomic Approaches to the Study of Pathophysiology of Diseases;142
7.1.1.2.1;Single Cell Proteomics for Personalized Medicine;142
7.1.1.2.2;Diseases Due to Misfolding of Proteins;143
7.1.1.2.2.1;Therapies for Protein Misfolding;143
7.1.1.2.3;Significance of Mitochondrial Proteome in Human Disease;144
7.1.1.3;Proteomic Technologies for Drug Discovery and Development;145
7.1.1.3.1;Role of Reverse-Phase Protein Microarray in Drug Discovery;145
7.1.1.3.2;Role of Proteomics in Clinical Drug Safety;145
7.1.1.3.3;Toxicoproteomics;146
7.1.1.4;Application of Pharmacoproteomics in Personalized Medicine;148
7.1.1.5;Summary;148
8;7.pdf;149
8.1;Chapter 7;149
8.1.1;Role of Metabolomics in Personalized Medicine;149
8.1.1.1;Metabolomics and Metabonomics;149
8.1.1.2;Metabolomics Bridges the Gap Between Genotype and Phenotype;150
8.1.1.3;Metabolomics, Biomarkers and Personalized Medicine;151
8.1.1.4;Metabolomic Technologies;151
8.1.1.4.1;Urinary Profiling by Capillary Electrophoresis;152
8.1.1.4.2;Lipid Profiling;153
8.1.1.4.3;Role of Metabolomics in Biomarker Identification and Pattern Recognition;153
8.1.1.4.4;Validation of Biomarkers in Large-Scale Human Metabolomics Studies;154
8.1.1.5;Pharmacometabonomics;154
8.1.1.6;Metabonomic Technologies for Toxicology Studies;155
8.1.1.7;Metabonomics/Metabolomics and Personalized Nutrition;156
8.1.1.8;Summary;156
9;8.pdf;157
9.1;Chapter 8;157
9.1.1;Personalized Biological Therapies;157
9.1.1.1;Introduction;157
9.1.1.2;Recombinant Human Proteins;157
9.1.1.3;Therapeutic Monoclonal Antibodies;158
9.1.1.4;Cell Therapy;158
9.1.1.4.1;Autologous Tissue and Cell Transplants;159
9.1.1.4.2;Stem Cells;159
9.1.1.4.2.1;Role of Stem Cells Derived from Unfertilized Embryos;159
9.1.1.4.3;Cloning and Personalized Cell Therapy;160
9.1.1.4.4;Use of Stem Cells for Drug Testing;160
9.1.1.5;Gene Therapy;160
9.1.1.6;Personalized Vaccines;161
9.1.1.6.1;Personalized Vaccines for Viral Diseases;161
9.1.1.6.2;Personalized Cancer Vaccines;162
9.1.1.6.2.1;Patient-Specific Cancer Vaccines;162
9.1.1.6.2.2;Antigen-Specific Vaccines;163
9.1.1.6.2.3;Autologous Cell Vaccines;163
9.1.1.6.2.4;Personalized Melanoma Vaccines;165
9.1.1.7;Antisense Therapy;165
9.1.1.7.1;RNA Interference;166
9.1.1.7.2;MicroRNAs;166
9.1.1.8;Summary;167
10;9.pdf;168
10.1;Chapter 9;168
10.1.1;Development of Personalized Medicine;168
10.1.1.1;Introduction;168
10.1.1.2;Non-genomic Factors in the Development of Personalized Medicine;169
10.1.1.2.1;Personalized Medicine Based on Circadian Rhythms;169
10.1.1.2.2;Intestinal Microflora;170
10.1.1.2.2.1;Gut Microbiome Compared to Human Genome;170
10.1.1.2.2.2;Metabolic Interactions of the Host and the Intestinal Microflora;171
10.1.1.2.3;Role of Drug Delivery in Personalized Medicine;171
10.1.1.2.4;Role of Molecular Imaging in Personalized Medicine;172
10.1.1.2.5;Personalized Approach to Clinical Trials;172
10.1.1.2.5.1;Use of Bayesian Approach in Clinical Trials;172
10.1.1.2.5.2;Individualizing Risks and Benefits in Clinical Trials;173
10.1.1.2.5.3;Clinical Trials of Therapeutics and Companion Diagnostics;174
10.1.1.3;Role of Genetic Banking Systems and Databases;174
10.1.1.3.1;Role of Biobanks in the Development of Personalized Medicine;174
10.1.1.3.2;UK Biobank;175
10.1.1.3.3;Biobanking and Development of Personalized Medicine in the EU;175
10.1.1.3.4;CARTaGENE for Biobanks in Canada;176
10.1.1.3.5;Personalized Medicine Based on PhysioGenomics™ Technology;177
10.1.1.4;Role of Bioinformatics in Development of Personalized Medicine;178
10.1.1.4.1;Health Information Management;179
10.1.1.4.1.1;Electronic Health Records;179
10.1.1.4.1.2;Linking Patient Medical Records and Genetic Information;180
10.1.1.4.1.3;Management of Personal Genomic Data;181
10.1.1.4.2;Personalized Prognosis of Disease;181
10.1.1.4.3;Integration of Technologies for Development of Personalized Medicine;182
10.1.1.5;Summary;182
11;10.pdf;183
11.1;Chapter 10;183
11.1.1;Personalized Therapy for Cancer;183
11.1.1.1;Introduction;183
11.1.1.1.1;Challenges of Cancer Classification;183
11.1.1.1.2;Relationships of Technologies for Personalized Management of Cancer;184
11.1.1.2;Impact of Molecular Diagnostics on the Management of Cancer;185
11.1.1.2.1;Analysis of RNA Splicing Events in Cancer;185
11.1.1.2.2;Analysis of Chromosomal Alterations in Cancer Cells;186
11.1.1.2.3;Cancer Classification Using Microarrays;186
11.1.1.2.4;Detection of Loss of Heterozygosity (LOH);187
11.1.1.2.5;Diagnosis of Cancer of an Unknown Primary;188
11.1.1.2.6;Diagnostics for Detection of Minimal Residual Disease (MRD);188
11.1.1.2.7;Fluorescent In Situ Hybridization;189
11.1.1.2.8;Gene Expression Profiling;189
11.1.1.2.9;Gene Expression Profiles Predict Chromosomal Instability in Tumors;190
11.1.1.2.10;Isolation and Characterization of Circulating Tumor Cells (CTCs);191
11.1.1.2.11;Modulation of CYP450 Activity for Cancer Therapy;191
11.1.1.2.12;Personalized Therapies Based on Oncogenic Pathway Signatures;192
11.1.1.2.13;Role of Molecular Imaging in Personalized Therapy of Cancer;193
11.1.1.2.13.1;Molecular Imaging for Personalized Drug Development in Oncology;193
11.1.1.2.13.2;Molecular Imaging as Guide to Cancer Treatment;194
11.1.1.2.13.3;Functional Diffusion MRI;195
11.1.1.2.13.4;Role of FDG-PET/CT in Personalizing Cancer Treatment;196
11.1.1.2.13.5;Tumor Imaging and Elimination by Targeted Gallium Corrole;197
11.1.1.2.14;Unraveling the Genetic Code of Cancer;197
11.1.1.3;Cancer Prognosis;198
11.1.1.3.1;Detection of Mutations for Risk Assessment and Prevention;199
11.1.1.4;Impact of Biomarkers on Management of Cancer;199
11.1.1.4.1;Predictive Biomarkers for Cancer;199
11.1.1.4.2;HER-2/neu Oncogene as a Biomarker for Cancer;200
11.1.1.4.3;l-asparaginase (l-ASP)Treatment of Cancer Guided by a Biomarker;200
11.1.1.5;Determination of Response to Therapy;201
11.1.1.5.1;Phenotype-Based Cell Culture Assays;201
11.1.1.5.2;Ex Vivo Testing of Tumor Biopsy for Chemotherapy Sensitivity;201
11.1.1.5.2.1;Genomic Approaches to Predict Response to Anticancer Agents;202
11.1.1.5.2.1.1;Gene Expression Patterns to Predict Response of Cancer to Therapy;202
11.1.1.5.2.1.2;Genomic Analysis of Tumor Biopsies;202
11.1.1.5.2.1.3;Mutation Detection at Molecular Level;203
11.1.1.5.2.1.4;Role of Genetic Variations in Susceptibility to Anticancer Drugs;203
11.1.1.5.3;Proteomic Analysis of Tumor Biopsies to Predict Response to Treatment;203
11.1.1.5.4;Real-time Apoptosis Monitoring;204
11.1.1.5.5;Serum Nucleosomes as Indicators of Sensitivity to Chemotherapy;204
11.1.1.5.6;Targeted Microbubbles to Tumors for Monitoring Anticancer Therapy;205
11.1.1.5.7;Tissue Systems Biology Approach to Personalized Management of Cancer;206
11.1.1.6;Targeted Cancer Therapies;206
11.1.1.6.1;Targeting Glycoproteins on Cell Surface;206
11.1.1.6.2;Targeting Pathways in Cancer;207
11.1.1.7;Functional Antibody-Based Personalized Therapies;207
11.1.1.8;Personalized Radiation Therapy;208
11.1.1.9;Molecular Diagnostics Combined with Cancer Therapeutics;209
11.1.1.9.1;Aptamers for Combined Diagnosis and Therapeutics of Cancer;210
11.1.1.10;Role of Nanobiotechnology in Personalized Management of Cancer;210
11.1.1.11;Design of Future Cancer Therapies;211
11.1.1.11.1;Screening for Personalized Anticancer Drugs;212
11.1.1.11.2;Role of Epigenetics in Development of Personalized Cancer Therapies;212
11.1.1.11.3;Personalized Therapy of Cancer Based on Cancer Stem Cells;213
11.1.1.12;Role of Oncoproteomics in Personalized Therapy of Cancer;213
11.1.1.12.1;Cancer Tissue Proteomics;214
11.1.1.13;Pharmacogenomic-Based Chemotherapy;215
11.1.1.13.1;Whole Genome Technology to Predict Drug Resistance;215
11.1.1.13.2;Anticancer Drug Selection Based on Molecular Characteristics of Tumor;215
11.1.1.13.3;Testing Microsatellite-Instability for Response to Chemotherapy;216
11.1.1.14;Pharmacogenetics of Cancer Chemotherapy;217
11.1.1.14.1;CYP1A2;217
11.1.1.14.2;Thiopurine Methyltransferase;218
11.1.1.14.3;Dihydropyrimidine Dehydrogenase;219
11.1.1.14.4;UGT1A1 Test as Guide to Irinotecan Therapy;219
11.1.1.15;Role of Computational Models in Personalized Anticancer Therapy;220
11.1.1.15.1;A Computational Model of Kinetically Tailored Treatment;220
11.1.1.15.2;Mathematical Modeling of Tumor Microenvironments;220
11.1.1.16;Molecular Profiling of Cancer;221
11.1.1.17;Drug Resistance in Cancer;222
11.1.1.17.1;Detection of Drug Resistance in Cancer by Metabolic Profiling;223
11.1.1.17.2;Determination of Chemotherapy Response by Topoisomerase Levels;223
11.1.1.17.3;A Systems Biology Approach to Drug Resistance in CRC;224
11.1.1.17.4;Management of Drug Resistance in Leukemia;224
11.1.1.17.5;Overexpression of Multidrug Resistance Gene;225
11.1.1.17.6;P53 Mutations;225
11.1.1.17.7;A Chemogenomic Approach to Drug Resistance;226
11.1.1.18;Examples of Personalized Management of Cancer;226
11.1.1.18.1;Personalized Management of Breast Cancer;226
11.1.1.18.1.1;Genetic Testing in Breast Cancer as a Guide to Treatment;227
11.1.1.18.1.2;Pharmacogenetics of Breast Cancer;228
11.1.1.18.1.3;Molecular Diagnostics in Breast Cancer;228
11.1.1.18.1.4;Racial Factors in the Management of Breast Cancer;230
11.1.1.18.1.5;Proteomics-Based Personalized Management of Breast Cancer;230
11.1.1.18.1.6;Tests for Prognosis of Breast Cancer;231
11.1.1.18.1.7;Developing Personalized Drugs for Breast Cancer;233
11.1.1.18.1.8;Developing Personalized Drugs for Triple-Negative Breast Cancer;234
11.1.1.18.1.9;Predicting Response to Chemotherapy in Breast Cancer;234
11.1.1.18.1.10;Prediction of Resistance to Therapy in Breast Cancer;237
11.1.1.18.1.11;Prediction of Adverse Reaction to RT in Breast Cancer;238
11.1.1.18.1.12;Prediction of Recurrence in Breast Cancer for Personalizing Therapy;238
11.1.1.18.1.13;TAILORx (Trial Assigning Individualized Options for Treatment);240
11.1.1.18.1.14;Gene Expression Plus Conventional Predictors of Breast Cancer;241
11.1.1.18.1.15;Future Development of Gene Expression Microarrays for Breast Cancer;242
11.1.1.18.2;Personalized Management of Ovarian Cancer;242
11.1.1.18.3;Personalized Management of Hematological Malignancies;245
11.1.1.18.3.1;Personalized Management of Acute Leukemias;245
11.1.1.18.3.2;Personalized Management of Chronic Lymphocytic Leukemia;247
11.1.1.18.3.3;Personalized Management of Multiple Myeloma (MM);247
11.1.1.18.3.4;Personalized Management B Cell Lymphomas;249
11.1.1.18.3.5;Personalized Vaccine for Follicular Lymphoma;249
11.1.1.18.3.6;Personalized Management of Myelodysplasia;250
11.1.1.18.4;Personalized Management of Malignant Melanoma;250
11.1.1.18.5;Personalized Management of Gastrointestinal Cancer;250
11.1.1.18.5.1;Personalized Management of Esophageal Cancer;250
11.1.1.18.5.2;Personalized Management of CRC;251
11.1.1.18.6;Personalized Management of Lung Cancer;254
11.1.1.18.6.1;Determination of Outcome of EGFR Tyrosine Kinase Inhibitor Treatment;254
11.1.1.18.6.2;Testing for Response to Chemotherapy in Lung Cancer;257
11.1.1.18.6.3;Testing for Prognosis of NSCLC;257
11.1.1.18.6.4;Testing for Recurrence of Lung Cancer;258
11.1.1.18.6.5;Role of a New Classification System in the Management of Lung Cancer;258
11.1.1.18.7;Personlized Management of Prostate Cancer;259
11.1.1.18.7.1;Benefit of Lifestyle Changes Shown by Gene Expression Studies;259
11.1.1.18.8;Personalized Management of Brain Cancer;260
11.1.1.18.8.1;Genetics and Genomics of Brain Cancer;260
11.1.1.18.8.2;Molecular Diagnostics for Personalized Management of Brain Cancer;262
11.1.1.18.8.3;Personalized Chemotherapy of Brain Tumors;264
11.1.1.18.8.4;Biosimulation Approach to Personalizing Treatment of Brain Cancer;265
11.1.1.18.8.5;Personalized Therapy of Oligodendroglial Tumors;266
11.1.1.18.8.6;Personalized Therapy of Neuroblastomas;267
11.1.1.18.8.7;Personalized Management of Germ Cell Brain Tumors;268
11.1.1.19;Future of Cancer Therapy;268
11.1.1.19.1;Challenges for Developing Personalized Cancer Therapies;268
11.1.1.19.2;The Cancer Genome Atlas;269
11.1.1.19.3;Role of the International Cancer Genome Consortium;269
11.1.1.19.4;Using Computer and Imaging Technologies to Personalize Cancer Treatment;271
11.1.1.19.5;Integrated Genome-Wide Analysis of Cancer for Personalized Therapy;271
11.1.1.20;Summary;272
12;11.pdf;273
12.1;Chapter 11;273
12.1.1;Personalized Management of Neurological Disorders;273
12.1.1.1;Introduction;273
12.1.1.2;Personalized Drug Development for Neurological Disorders;273
12.1.1.2.1;Personalized Drug Discovery;273
12.1.1.2.2;Molecular Imaging and CNS Drug Development;273
12.1.1.3;Personalized Management of AD;275
12.1.1.4;Personalized Management of PD;276
12.1.1.4.1;Discovery of Subgroup-Selective Drug Targets in PD;277
12.1.1.5;Personalized Management of Epilepsy;277
12.1.1.5.1;Choice of the Right AED;278
12.1.1.5.1.1;Pharmacogenetics of Epilepsy;278
12.1.1.5.2;Pharmacogenomics of Epilepsy;279
12.1.1.5.3;Drug Resistance in Epilepsy;280
12.1.1.5.4;Future Prospects for Epilepsy;281
12.1.1.6;Personalized Management of Migraine;282
12.1.1.7;Personalized Treatment of MS;282
12.1.1.7.1;MBP8298;283
12.1.1.7.1.1;Pharmacogenomics of IFN-b Therapy in MS;284
12.1.1.7.1.2;Future Prospects of Personalized Therapy of MS;285
12.1.1.8;Personalized Management of Psychiatric Disorders;285
12.1.1.8.1;Psychopharmacogenetics;285
12.1.1.8.1.1;COMT Genotype and Response to Amphetamine;286
12.1.1.8.1.2;Genotype and Response to Methylphenidate in Children with ADHD;286
12.1.1.8.2;Personalized Antipsychotic Therapy;287
12.1.1.8.3;Personalized Antidepressant Therapy;290
12.1.1.8.3.1;Pretreatment EEG to Predict Adverse Effects to Antidepressants;291
12.1.1.8.3.2;Individualization of SSRI Treatment;291
12.1.1.8.3.3;Vilazodone with a Test for Personalized Treatment of Depression;293
12.1.1.9;Summary;293
13;12.pdf;294
13.1;Chapter 12;294
13.1.1;Personalized Therapy of Cardiovascular Diseases;294
13.1.1.1;Introduction;294
13.1.1.2;Role of Cardiovascular Diagnostics in Personalized Management;294
13.1.1.2.1;Testing in Coronary Heart Disease;294
13.1.1.2.2;SNP Genotyping in Cardiovascular Disorders;295
13.1.1.2.3;Cardiovascular Disorders with a Genetic Component;296
13.1.1.2.3.1;Gene Variant as a Risk Factor for Sudden Cardiac Death;298
13.1.1.2.3.2;SNP Chip for Study of Cardiovascular Diseases;299
13.1.1.2.4;Pharmacogenomics of Cardiovascular Disorders;299
13.1.1.2.5;Modifying the Genetic Risk for MI;300
13.1.1.2.6;Management of Heart Failure;300
13.1.1.2.6.1;b-Blockers;300
13.1.1.2.6.2;Bucindolol;301
13.1.1.2.6.3;BiDil;301
13.1.1.2.7;Management of Hypertension;302
13.1.1.2.7.1;Pharmacogenomics of Diuretic Drugs;303
13.1.1.2.7.2;Pharmacogenomics of ACE Inhibitors;304
13.1.1.2.7.3;Management of Hypertension by Personalized Approach;304
13.1.1.2.8;Pharmacogenetics of Lipid-Lowering Therapies;305
13.1.1.2.8.1;Polymorphisms in Genes Involved in Cholesterol Metabolism;305
13.1.1.2.8.2;Role of eNOS Gene Polymorphisms;306
13.1.1.2.8.3;The STRENGTH Study;307
13.1.1.2.8.4;Personalized Management of Women with Hyperlipidemia;308
13.1.1.2.9;Thrombotic Disorders;308
13.1.1.2.9.1;Factor V Leiden Mutation;308
13.1.1.2.9.2;Anticoagulant Therapy;309
13.1.1.2.10;Nanotechnology-Based Personalized Therapy of Cardiovascular Diseases;310
13.1.1.2.11;Project euHeart for Personalized Management of Cardiovascular Diseases;311
13.1.1.2.12;Concluding Remarks;311
13.1.1.3;Summary;312
14;13.pdf;313
14.1;Chapter 13;313
14.1.1;Personalized Management of Miscellaneous Disorders;313
14.1.1.1;Management of Viral Infections;313
14.1.1.1.1;Management of HIV;313
14.1.1.1.1.1;Genetics of Human Susceptibility to HIV Infection;313
14.1.1.1.1.2;Pharmacogenomics of Antiretroviral Agents;314
14.1.1.1.1.3;Role of Diagnostic Testing in HIV;315
14.1.1.1.1.4;CD4 Counts as a Guide to Drug Therapy for AIDS;315
14.1.1.1.1.5;Drug-Resistance in HIV;315
14.1.1.1.1.6;Measurement of Replication Capacity;316
14.1.1.1.1.7;Prevention of Adverse Reactions to Antiviral Drugs;316
14.1.1.1.1.8;Role of Genetic Variations in Susceptibility to HIV-1;317
14.1.1.1.1.9;Pharmacogenetics and HIV Drug Safety;318
14.1.1.1.2;Treatment of Hepatitis B;318
14.1.1.1.3;Treatment of Hepatitis C;318
14.1.1.2;Personalized Management of Tuberculosis (TB);320
14.1.1.3;Personalized Management of Skin Disorders;321
14.1.1.4;Personalized Therapy of Rheumatoid Arthritis (RA);321
14.1.1.4.1;DIATSTATTM Anti-Cyclic Citrullinated Peptides in RA;323
14.1.1.4.2;Personalization of COX-2 Inhibitor Therapy;323
14.1.1.4.3;Personalization of Infliximab Therapy;324
14.1.1.5;Personalized Therapy of Asthma;324
14.1.1.5.1;Genetic Polymorphism and Response to b2-Adrenergic Agonists;324
14.1.1.5.2;Genotyping in Asthma;325
14.1.1.6;Personalized Approaches in Immunology;326
14.1.1.6.1;Pharmacogenetics and Pharmacogenomics of Immunosuppressive Agents;327
14.1.1.6.2;Personalized Immunosuppressant Therapy in Organ Transplants;327
14.1.1.7;Personalized Management of Pain;328
14.1.1.7.1;Pharmacogenetics/Pharmacogenomics of Pain;329
14.1.1.7.2;Mechanism-Specific Management of Pain;330
14.1.1.7.3;Preoperative Testing to Tailor Postoperative Analgesic Requirements;330
14.1.1.7.4;Personalized Analgesics;331
14.1.1.8;Management of Genetic Disorders;332
14.1.1.8.1;Personalized Treatment of Cystic Fibrosis;332
14.1.1.9;Personalized Management of Gastrointestinal Disorders;333
14.1.1.9.1;Personalized Therapy of Inflammatory Bowel Disease;333
14.1.1.9.2;Personalized Management of Lactose Intolerance;334
14.1.1.10;Personalized Approach to Addiction;334
14.1.1.10.1;Genetic Polymorphism and Management of Alcoholism;334
14.1.1.10.2;Personalized Therapy for Smoking Cessation;335
14.1.1.10.2.1;Antidepressant Therapy for Smoking Cessation;335
14.1.1.10.2.2;Effectiveness of Nicotine Patches in Relation to Genotype;335
14.1.1.10.3;Personalized Approach to Drug Addiction;336
14.1.1.11;Personalized Approaches to Miscellaneous Problems;336
14.1.1.11.1;Hormone Replacement Therapy in Women;336
14.1.1.11.2;Personalized Treatment of Malaria;337
14.1.1.11.3;Personalized Management of Renal Disease;338
14.1.1.11.4;Personalization of Organ Transplantation;338
14.1.1.11.4.1;Personalization of Kidney Transplantation;339
14.1.1.11.4.2;Personalization of Cardiac Transplantation;339
14.1.1.11.4.3;Prediction of Rejection to Tailor Anti-Rejection Medications;340
14.1.1.11.4.4;Role of Immunological Biomarkers in Monitoring Grafted Patients;341
14.1.1.11.4.5;Improved Matching of Blood Transfusion;341
14.1.1.11.5;Personalized Care of Trauma Patients;342
14.1.1.11.6;Personalized Anticoagulation;342
14.1.1.11.7;Personalized Hyperbaric Oxygen Therapy;343
14.1.1.12;Summary;344
15;14.pdf;345
15.1;Chapter 14;345
15.1.1;Personalized Preventive Medicine;345
15.1.1.1;Introduction;345
15.1.1.2;Personalized Nutrition;346
15.1.1.2.1;Nutrigenomics;346
15.1.1.2.1.1;Nutrigenomics and Functional Foods;347
15.1.1.2.1.2;Nutrigenomics and Personalized Medicine;348
15.1.1.2.2;Nutrition and Proteomics;348
15.1.1.2.3;Personalized Diet Prescription;349
15.1.1.3;Summary;349
16;15.pdf;350
16.1;Chapter 15;350
16.1.1;Organization of Personalized Medicine;350
16.1.1.1;Players in the Development of Personalized Medicine;350
16.1.1.1.1;Personalized Medicine Coalition;350
16.1.1.1.2;Role of Pharmaceutical Industry;351
16.1.1.1.2.1;Production and Distribution of Personalized Medicines;353
16.1.1.1.3;Role of Biotechnology Companies;354
16.1.1.1.4;Role of life Sciences Industries;354
16.1.1.1.5;Collaboration Between the Industry and the Academia;355
16.1.1.1.6;Role of the Clinical Laboratories;355
16.1.1.1.7;Role of the US Government;356
16.1.1.1.8;Role of US Government Institutions in Development of Personalized Medicine;357
16.1.1.1.8.1;NIH’s Roadmap Initiative for Medical Research;357
16.1.1.1.8.2;NIH and Personalized Medicine;358
16.1.1.1.8.3;National Institute of General Medical Sciences;358
16.1.1.1.8.4;National Institute of Standards and Technology;359
16.1.1.1.9;Role of Academic Institutions in the USA;360
16.1.1.1.9.1;Clinical Proteomics Program;360
16.1.1.1.9.2;Coriell Personalized Medicine Collaborative™;360
16.1.1.1.9.3;Delaware Valley Personalized Medicine Project;361
16.1.1.1.9.4;Evaluation of Genetic Tests and Genomic Applications;362
16.1.1.1.9.5;Genomic-Based Prospective Medicine Project;362
16.1.1.1.9.6;Personalized oncology at Massachusetts General Hospital;363
16.1.1.1.9.7;Pharmacogenetics Research Network and Knowledge Base;364
16.1.1.1.9.8;Quebec Center of Excellence in Personalized Medicine;364
16.1.1.1.9.9;Southeast Nebraska Cancer Center’s Personalized Medicine Network;365
16.1.1.1.9.10;Wisconsin Genomics Initiative;365
16.1.1.1.10;Role of Healthcare Organizations and Hospitals;365
16.1.1.1.10.1;Signature Genetics;366
16.1.1.1.10.2;The Mayo Clinic Genetic Database;366
16.1.1.1.10.3;Research Center for Personalized Medicine at Mt. Sinai Medical Center;367
16.1.1.1.11;Role of the Medical Profession;367
16.1.1.1.11.1;Education of the Physicians;367
16.1.1.1.11.2;Off-Label Prescribing and Personalized Medicine;368
16.1.1.1.11.3;Medical Education;368
16.1.1.1.12;Education of the Public;369
16.1.1.1.12.1;Role of the Internet in Development of Personalized Medicine;369
16.1.1.1.12.2;Public Attitude Towards Personalized Medicine;370
16.1.1.2;Global Scope of Personalized Medicine;371
16.1.1.2.1;Personalized Medicine in the Developed Countries;371
16.1.1.2.1.1;US HHSs Supports Personalized Medicine;371
16.1.1.2.1.2;Personalized Medicine in the USA;372
16.1.1.2.1.3;Personalized Medicine in the EU;372
16.1.1.2.1.4;UK National Health Service and Medical Genetics;373
16.1.1.2.2;Personalized Medicine in the Developing Countries;373
16.1.1.3;Advantages and Limitations of Personalized Medicine;374
16.1.1.4;Summary;376
17;16.pdf;377
17.1;Chapter 16;377
17.1.1;Ethical and Regulatory Aspects of Personalized Medicine;377
17.1.1.1;Introduction to Ethical Issues;377
17.1.1.1.1;Ethical Issues of Pharmacogenetics;377
17.1.1.1.2;Ethical Aspects of Genetic Information;378
17.1.1.1.2.1;Ethical Issues of Whole Genome Analysis;378
17.1.1.1.2.2;Ethical Aspects of Direct-to-Consumer (DTC) Genetic Services;379
17.1.1.1.2.3;Privacy Issues in Personalized Medicine;381
17.1.1.1.2.4;Genetic Information Nondiscrimination Act in the USA;381
17.1.1.1.3;Genotype-Specific Clinical Trials;382
17.1.1.1.4;Social Issues in Personalized Medicine;382
17.1.1.1.4.1;Race and Personalized Medicine;383
17.1.1.2;Regulatory Aspects;385
17.1.1.2.1;CLSI Guideline for the Use of RNA Controls in Gene Expression Assays;386
17.1.1.2.2;Microarray Quality Control Project;386
17.1.1.2.3;Regulatory Aspects of Pharmacogenetics;387
17.1.1.2.4;Regulation of DTC Genetic Testing;388
17.1.1.2.5;FDA and Pharmacogenomics;389
17.1.1.2.5.1;FDA Guidance for Pharmacogenomic Data Submissions;389
17.1.1.2.5.2;Joint Guidelines of the FDA and EU Regulators for Pharmacogenomics;390
17.1.1.2.6;Pharmacogenomic Information in Drug Labels;390
17.1.1.2.7;FDA guidelines for Pharmacogenomics-Based Dosing;391
17.1.1.2.8;FDA and Validation of Biomarkers;391
17.1.1.2.8.1;FDA and Predictive Medicine;392
17.1.1.2.8.2;FDA Regulation of Multivariate Index Assays;393
17.1.1.2.8.3;Evaluation of Companion Diagnostics/Therapeutic for Cancer;395
17.1.1.3;Summary;395
18;17.pdf;396
19;18.pdf;407
19.1;Chapter 18;407
19.1.1;Future of Personalized Medicine;407
19.1.1.1;Introduction;407
19.1.1.1.1;Ongoing Genomic Projects;408
19.1.1.1.1.1;Understanding the Genetic Basis of Diseases;408
19.1.1.1.1.2;Personal Genome Project;408
19.1.1.1.1.3;Genome-Wide Association Studies;409
19.1.1.1.1.4;The 1000 Genomes Project;410
19.1.1.1.1.5;Genomics of Aging in a Genetically Homogeneous Population;411
19.1.1.1.2;Translational Science and Personalized Medicine;411
19.1.1.1.2.1;Translation of Genomic Research into Genetic Testing for Healthcare;411
19.1.1.1.2.2;Long-Term Behavioral Effects of Personal Genetic Testing;412
19.1.1.2;Drivers for the Development of Personalized Medicine;413
19.1.1.2.1;Evolution of Medicine as a Driver for Personalized Therapy Markets;414
19.1.1.2.2;Personalized Predictive Medicine;414
19.1.1.3;Opportunities and Challenges;415
19.1.1.3.1;Prospects and Limitations of Genetic Testing;415
19.1.1.3.2;Challenges in Delivery of Personalized Medicine;416
19.1.1.3.3;Pharmacotyping;417
19.1.1.3.4;Concluding Remarks about the Future of Personalized Medicine;417
19.1.1.4;Summary;418
20;BM2.pdf;419
20.1;Anchor 1;419