Textbook of personalized medicine:
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| Format: | Buch |
| Sprache: | English |
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Cham, Switzerland
Springer
[2021]
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| Ausgabe: | Third edition |
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| Online-Zugang: | Inhaltsverzeichnis Klappentext |
| Beschreibung: | xliii, 744 Seiten Diagramme |
| ISBN: | 9783030620790 |
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| 245 | 1 | 0 | |a Textbook of personalized medicine |c Kewal K. Jain |
| 250 | |a Third edition | ||
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| 650 | 4 | |a Pharmacotherapy | |
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| 650 | 4 | |a Medicine | |
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Datensatz im Suchindex
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| adam_text | Contents 1 Basic Aspects.............................................................................. Definition of Personalized Medicine.......................................... Personalized Medicine as 1 OP Medicine................................ History of Medical Concepts Relevant to Personalized Medicine...................................................................................... Evolution of Modern Personalized Medicine.......................... Molecular Biological Basis of Personalized Medicine................ The Human Genome................................................................ Chromosomes.......................................................................... Genes........................................................................................ Genetic Variations in the Human Genome.............................. Mitochondrial tRNA and Personalized Medicine.................... Molecular Pathology................................................................ Basics Technologies for Developing Personalized Medicine.... Definitions of Technologies Relevant to Personalized Medicine.................................................................................. Problems with the ICH Definitions of Pharmacogenomics and Pharmacogenetics.............................................................. Omics’ and Personalized Medicine............................................ Relationship of Various Technologies to Personalized Medicine.................................................................................. Conventional Medicine
Versus Personalized Medicine.............. Personalized Medicine and Evidence-Based Medicine.............. Role of Genetics in Future Approaches to Healthcare................ Genetic Medicine.................................................................... Human Disease and Genes...................................................... Genetic and Environmental Interactions in Etiology of Human Diseases.................................................................. Role of Genetics in Development of Personalized Medicines................................................................................ Role of Epigenetics in Personalized Medicine........................ Role of Systems Biology in Personalized Medicine.................... Systems Pharmacology............................................................ Systems Medicine.................................................................... Synthetic Biology and Development of Personalized Medicines.................................................................................... Personalized Digital Medicine.................................................... Artificial Intelligence in Personalized Medicine...................... 1 1 3 3 5 5 5 7 7 8 16 16 17 17 18 18 18 18 19 20 20 20 21 21 23 24 25 25 27 28 28 xi
Contents xii 2 Machine Learning and Personalized Medicine.......................... Algorithms Based on Machine Learning.................................. Bioelectronics and Personalized Medicine................................ A Personalized Approach to Environmental Factors in Disease......................................................................................... Role of Animal Models in Development of Personalized Medicine........................................................................................... Animal Models for Supplementing Research on Human Genomes....................................................................................... Mouse Models for Personalized Medicine................................ Promise and Limitations of Animal Models for Personalized Medicine....................................................................................... Role of Pets with Naturally Occuring Diseases........................ Reclassification of Diseases............................................................ Translational Science and Personalized Medicine........................ Genome to Phenome Translation............................................... Personalization of Multimodal Therapies...................................... Applications of Personalized Medicine in Various Therapeutic Areas.................................................................................................. References......................................................................................... 29 29 29 Molecular Diagnostics in Personalized
Medicine..................... Introduction....................................................................................... Molecular Diagnostic Technologies............................................... DirectLinear™ Analysis.............................................................. Denaturing High-Performance Liquid Chromatography........ Multiplex Allele-Specific Diagnostic Assay.............................. Restriction Fragment Length Polymorphism (RFLP)............... Real-Time PCR for Detection of CNVs.................................... Non-PCR Methods...................................................................... DNA Sequencing........................................................................ Emerging Sequencing Technologies........................................... Ion Torrent’s Sequencing Technology........................................ Biochips and Microarrays................................................................ Role of Biochip/Microarray Technology in Personalized Medicine....................................................................................... Applications of Biochip/Microarray Technology in Personalized Medicine........................................................... Standardizing the Microarrays................................................... Biochip Technologies.................................................................. Microfluidics................................................................................ Electronic Detection of Nucleic Acids on Microarrays........... Strand
Displacement Amplification on a Biochip..................... Rolling Circle Amplification on DNA Microarrays................. Universal DNA Microarray Combining PCR and Ligase Detection Reaction...................................................................... Protein Biochips.......................................................................... SNP Genotyping.............................................................................. Genotyping and Haplotyping..................................................... Technologies for SNP Analysis................................................. 39 39 39 41 41 41 41 42 42 43 44 48 60 30 30 31 31 32 32 33 34 34 34 34 35 60 61 61 62 63 65 66 66 66 67 70 71 75
xiii Contents ay-Based Detection of SNPs.................................................... Electrochemical DNA Probes.......................................... . ■. · Laboratory Multiple Analyte Profile........................................ PCR-CTPP (Confronting Two-Pair Primers).......................... TaqMan Real-Time PCR.......................................................... Locked Nucleic Acid................................................................ Molecular Inversion Probe Based Assays................................ Pyrosequencing........................................................................ Smart Amplification Process Version 2.................................... Zinc Finger Proteins................................................................ Mitochondrial SNPs................................................................ Limitations of SNP in Genetic Testing.................................... Concluding Remarks on SNP Genotyping.............................. Impact of SNPs on Personalized Medicine.............................. Detection of Copy Number Variations........................................ CNVer Algorithm for CNV Detection.................................... CNVnator for Discovery of CNVs and Genotyping................ Study of Rare Variants in Pinpointing Disease-Causing Genes............................................................................................ Optical Mapping.......................................................................... Proteomics in Molecular
Diagnosis............................................ Layered Gene Scanning.......................................................... Comparison of Proteomic and Genomic Approaches in Personalized Medicine........................................................ Role of Biosensors in Personalized Medicine............................ Gene Expression Profiling.......................................................... DNA Microarrays.................................................................... Analysis of Single-Cell Gene Expression................................ Gene Expression Profiling Based on Alternative RNA Splicing.................................................................................... Whole Genome Expression Array.......................................... Tangerine™ Expression Profiling............................................ Gene Expression Analysis on Biopsy Samples........................ Profiling Gene Expression Patterns of White Blood Cells .... Serial Analysis of Gene Expression (SAGE).......................... Multiplexed Molecular Profiling.............................................. Gene Expression Analysis Using Competitive PCR and MALDI TOF MS.............................................................. Monitoring In Vivo Gene Expression by Molecular Imaging.................................................................................... Molecular Imaging and Personalized Medicine.......................... Combination of Diagnostics and Therapeutics............................ Use of Molecular Diagnostics for Stratification in
Clinical Trials........................................................................................ Companion Diagnostics.......................................................... Companies Involved in Companion Diagnostics.................... Point-of-Care Diagnosis.............................................................. Point-of-Care Diagnosis of Infections.................................... Advantages Versus Disadvantages of Point-of-Care Diagnosis.................................................................................. 75 77 77 77 78 78 78 78 79 79 79 80 80 81 81 81 81 82 82 83 83 84 84 85 86 86 87 88 88 88 89 89 90 90 91 91 91 92 92 92 93 94 95
Contents XIV Future of Point-of-Care Diagnosis............................................. Genetic Testing for Disease Predisposition.................................. Preventive Genetics by Early Diagnosis of Mitochondrial Diseases......................................................................................... Direct-to-Consumer Genetic Services...................................... Personalized Polygenic Risk Scores........................................... Role of Diagnostics in Integrated Healthcare................................ Concept of Integrated Healthcare............................................... Components of Integrated Healthcare........................................ Advantages and Limitations of Integrated Healthcare............. Commercially Available Systems for Integrated Healthcare .. Future of Molecular Diagnostics in Personalized Medicine........ References......................................................................................... 3 4 95 96 96 96 97 97 97 98 99 100 100 100 Role of Biomarkers in Personalized Medicine.......................... Introduction....................................................................................... Definitions..................................................................................... Biomarker as a Response to Therapeutic Intervention............. Pharmacokinetic/Pharmacodynamics Biomarkers................... Predictive В iomarkers.................................................................. Biomarkers of Drug
Safety......................................................... Applications of Biomarkers........................................................... Diagnostic Applications of Biomarkers.................................... Applications of Biomarkers for Targeted Therapies................. Proteomic Strategies for Biomarker Identification................... Proteomic Technologies for Detection of Biomarkers in Body Fluids.............................................................................. Protein Patterns............................................................................ Biomarkers for Diagnostics....................................................... Biomarkers for Drug Development............................................. Role of Biomarkers in Development of Personalized Drugs .... Bioinformatics to Sort Biomarker Data for Personalized Medicine........................................................................................... Use of Bayesian Approach in Biomarker-Based Clinical Trials.............................................................................. Biomarkers for Monitoring Response to Therapy........................ Drug Rescue by Biomarker-Based Personalized Medicine........ Biobanking, Biomarkers and Personalized Medicine in EU .... Biomarkers Consortium Personalized Medicine..................... Future Role of Biomarkers in Personalized Medicine................. References......................................................................................... 103 103 103 104 104 104 105 105 105 106 107
Pharmacogenetics.......................................................................... Basics of Pharmacogenetics........................................................... Role of Molecular Diagnostics in Pharmacogenetics................... Role of Pharmacogenetics in Pharmaceutical Industry............... Study of the Drug Metabolism and Pharmacological Effects.. Causes of Variations in Drug Metabolism................................ Enzymes Relevant to Drug Metabolism.................................... Pharmacogenetics of Phase I Metabolism................................ 115 115 116 116 117 118 118 119 107 108 108 108 108 109 109 110 Ill Ill 112 112 113
Contents XV 5 Pharmacogenetics of Phase II Metabolism.............................. Measurement of CYP Isoforms.............................................. Polymorphism of Drug Transporters...................................... Genetic Variation in Drug Targets............................................ Effect of Genetic Polymorphisms on Disease Response to Drugs.................................................................................... Ethnic Differences in Drug Metabolism.................................. Gender Differences in Pharmacogenetics................................ Role of Pharmacogenetics in Drug Safety.............................. Therapeutic Drug Monitoring, Phenotyping, and Genotyping. Phenomics................................................................................ Molecular Toxicology in Relation to Personalized Medicines. Pharmacogenetics in Clinical Trials........................................ Postmarketing Pharmacogenetics............................................ Clinical Implications of Pharmacogenetics................................ HLA Alleles Associated with Lumiracoxib-Related Liver Injury........................................................................................ Pharmacogenomic Biomarker Information in Drug Labels ... Pharmacogenetic Basis of Thiopurine Toxicity...................... Tranilast-Induced Hyperbilirubinemia Due to Gene Polymorphism.......................................................................... Standardized Terminology for Clinical Pharmacogenetic Test
Results.............................................................................. Use of Pharmacogenetics in Personalized Medicine.............. Linking Pharmacogenetics with Pharmacovigilance.............. Recommendations for the Clinical Use of Pharmacogenetics . Limitations of Pharmacogenetics................................................ Pharmacoepigenomics Versus Pharmacogenetics in Drug Safety.......................................................................................... Future Role of Pharmacogenetics in Personalized Medicine .... References.................................................................................... 123 124 125 125 Pharmacogenomics.................................................................... Introduction.................................................................................. Basics of Pharmacogenomics...................................................... Pharmacogenomics and Drug Discovery.................................... Preclinical Prediction of Drug Efficacy.................................. Role of Pharmacogenomics in Drug Discovery and Drug Delivery.................................................................................... Next Generation Sequencing and Pharmacogenomics................ Pharmacogenomics and Clinical Trials........................................ Impact of Genetic Profiling on Clinical Studies...................... Limitations of the Pharmacogenomic-Based Clinical Trials .. Pharmacogenomic Aspects of Major Therapeutic Areas............
Oncogenomics.......................................................................... Cardiogenomics...................................................................... Neuropharmacogenomics........................................................ Current State and Future of Pharmacogenomics........................ References.................................................................................... 153 153 153 154 156 125 126 127 128 136 138 139 140 141 141 141 142 146 147 147 147 149 150 150 151 151 152 156 156 156 157 158 159 159 161 162 165 166
Contents XVI 6 7 8 Role of Pharmacoproteomics....................................................... Basics of Proteomics........................................................................ Proteomic Approaches to the Study of Pathophysiology of Diseases....................................................................................... Single Cell Proteomics for Personalized Medicine................. Diseases Due to Misfolding of Proteins.................................... Therapies for Protein Misfolding............................................... Significance of Mitochondrial Proteome in Human Disease .. Proteomic Technologies for Drug Discovery and Development.. Proteins and Drug Action........................................................... Role of Reverse-Phase Protein Microarray in Drug Discovery..................................................................................... Role of Proteomics in Clinical Drug Safety.............................. Toxicoproteomics........................................................................ Role of Protein Biochips in Personalized Medicine................. Role of Nanoproteomics in Personalized Medicine................. Applications of Pharmacoproteomics in Personalized Medicine........................................................................................... Proteomic Biomarkers and Personalized Medicine................. Role of Proteomics-Based Molecular Diagnostics in Personalized Medicine...........................................................
References......................................................................................... 167 167 168 169 169 169 170 171 171 171 171 172 173 173 174 174 175 175 Role of Metabolomics in Personalized Medicine..................... Metabolomics and Metabonomics................................................. Metabolome Database...................................................................... Metabolomics Bridges the Gap Between Genotype and Phenotype................................................................................... Metabolomic Technologies............................................................. Lipid Profiling.............................................................................. Applications Relevant to Personalized Medicine.......................... Pharmacometabolomics/Pharmacometabonomics................... Metabonomic Technologies for Toxicology Studies................. Metabolomics and Biomarkers................................................... Metabonomics/Metabolomics and Personalized Nutrition.... Metabolomics for Personalized Medicine................................ References......................................................................................... 177 177 177 Non-genomic Aspects of Personalized Medicine..................... Introduction....................................................................................... Non-genomic Factors in Response to Drugs................................ Personalized Medicine Based on Circadian Rhythms................. Cytomics as a Basis for Personalized
Medicine............................ Intestinal Microflora and Personalized Medicine.......................... Gut Microbiome Compared to Human Genome....................... Metabolic Interactions of the Host and the Intestinal Microflora..................................................................................... Role of Drug Delivery in Personalized Medicine.......................... Role of Nanobiotechnology in Personalized Medicine............... Role of Nanobiotechnology in Molecular Diagnostics............. 185 185 185 186 187 187 187 178 178 179 180 180 180 181 182 183 183 188 188 189 189
Contents xvii Nanobiotechnology for Therapeutics Design and Monitoring............................................................................. Nanobiotechnology for Therapeutic Applications................... References......................................................................................... 190 191 193 9 Personalized Biological Therapies............................................... Introduction....................................................................................... Recombinant Human Proteins....................................................... Therapeutic Monoclonal Antibodies............................................... Cell Therapy..................................................................................... Autologous Tissue and Cell Transplants.................................... Stem Cells..................................................................................... Cloning and Personalized Cell Therapy.................................... Use of Stem Cells for Drug Testing........................................... Gene Therapy................................................................................... Gene Editing by CRISPR/Cas9 System.................................... Personalized Gene Therapy for Cancer.................................... Personalized Vaccines...................................................................... Personalized Vaccines for Viral Diseases.................................. Personalized Cancer Vaccines..................................................... Antisense
Therapy............................................................................. RNA Interference......................................................................... MicroRNAs................................................................................... References.......................................................................................... 195 195 195 195 196 196 196 197 197 198 198 199 199 199 200 200 200 201 201 10 Personalized Complementary Alternative Therapies........ Introduction....................................................................................... Ayurveda as a Personalized Healthcare System....................... Taditional Chinese Medicine..................................................... Personalized Hyperbaric Oxygen Therapy.................................... Personalized Nutrition.................................................................... Nutrigenomics............................................................................... Nutrigenetics and Personalized Medicine.................................. Personalized Diet Prescription................................................... Role of Systems Medicine in Personalized Nutrition............... Personalized Physical Exercise....................................................... Aerobic Exercise Response Variations in Individuals............... Exercise-Induced Muscle Hypertrophy and Strength Variations..................................................................................... Personalized Exercise for Prevention of Functional Decline in the
Elderly.................................................................. References.......................................................................................... 203 203 203 203 204 205 206 208 209 210 211 211 Personalized Therapy of Neurological Disorders..................... Introduction....................................................................................... Individuality of the Human Brain as a Basis of Personalized Neurology..................................................................................... Gender Differences in Neurological Disorders.......................... Measuring Brain Health across Life Span................................ AI for Personalized Neurology................................................... 213 213 11 211 212 212 213 214 214 215
Contents xviii 12 Personalized Management of Alzheimer’s Disease................. Personalized Management of Parkinson’s Disease................... Personalized Management of Huntington Disease................... Personalized Management of Amyotrophic Lateral Sclerosis....................................................................................... Personalized Management of Epilepsy...................................... Personalized Management of Migraine.................................... Personalized Management of Intracranial Aneurysms............. Personalized Management of Stroke........................................ Personalized Treatment of Multiple Sclerosis.......................... Personalized Management of Traumatic Brain Injury............. Personalized Management of Myasthenia Gravis................ Personalized Management of Tinnitus...................................... Personalized Management of Pain............................................. Personalized Management of Sleep Disorders.......................... Future of Personalized Neurology............................................. References......................................................................................... 215 217 221 Personalized Therapy of Psychiatric Disorders........................ Introduction....................................................................................... Role of Amygdala in Personalized Psychiatry.............................. Gene Polymorphisms as Basis of Personalized Approach to Psychiatric
Disorders.................................................................. Psychopharmacogenetics/Psychopharmacodynamics................. Serotonin Genes.......................................................................... Calcium Channel Gene................................................................ Dopamine Receptor Genes......................................................... COMT Genotype and Response to Amphetamine................... Methylenetetrahydrofolate Reductase...................................... Genetic Loci Associated with Risk of Major Depressive Disorder......................................................................................... Role of Gene Mutations in ADHD............................................. Genotype and Response to Methylphenidate in Children with ADHD................................................................................... GeneSight Tests for Individualized Therapy of Psychiatric Disorders....................................................................................... Personalized Antipsychotic Therapy for Schizophrenia............... Pharmacogenetics for Personalizing Antipsychotic Therapy .. Patient-Derived Stem Cells for Personalizing Drugs for Schizophrenia.............................................................................. Personalized Therapy of Bipolar Disorder.................................... Personalized Antidepressant Therapy............................................. Pharmacogenetics/Pharmacogenomics of Antidepressant
Therapy......................................................................................... Biomarkers of Response to Antidepressant Treatment............. EEG Biomarkers for Predicting Safety and Efficacy of Antidepressants............................................................................ GeneSight Pharmacogenomic Test............................................. Individualization of SSRI Treatment........................................ 263 263 263 222 222 231 233 234 241 247 249 249 250 256 258 258 263 264 264 264 265 265 265 266 266 266 266 267 267 269 269 269 270 271 271 272 273
XIX Contents Role of Protein sFRP3 in Predicting Response to Antidepressants.................................................................... Treatment of Depression Guided by Pharmacogenetics.......... Vilazodone with a Test for Personalized Treatment of Depression.......................................................................... Personalized Management of Alcohol Use Disorder.................. Personalized Management of Autism Spectrum Disorders........ References.................................................................................... 13 14 Personalized Therapy of Cardiovascular Disorders.............. Cardiovascular Disorders............................................................ Role of Diagnostics in Personalized Management of Cardiovascular Disease........................................................ Assessing Patients with Coronary Heart Disease.................... Assessing Coronary Artery Disease for Percutaneous Coronary Interventions............................................................ Companion Diagnostics for Therapy of Cardiovascular Disorders.................................................................................. Biomarkers and Personalized Management of Cardiovascular Disorders.................................................................................. Pharmacogenomics of Cardiovascular Disorders.................... Nanotechnology-Based Personalized Therapy of Cardiovascular Diseases.......................................................... Personalized Management of Chronic Myocardial Ischemia..
Personalized Management of Myocardial Infarction.................. Management of Heart Failure.................................................. Management of Atrial Fibrillation.......................................... Management of Hypertension.................................................. Personalized Lipid-Lowering Therapies.................................. Thrombotic Disorders.............................................................. Personalized Management of Aortic Aneurysms.................... Clinical Trials of Personalized Therapy of Cardiovascular Diseases.................................................................................... Project euHeart for Personalized Management of Heart Disease.................................................................................... Modification of Life Style Factors in Management of Cardiovascular Disorders.................................................... Multimorbidity in Patients with Cardiovascular Disease........ Systems Biology Approach to Personalized Cardiology........ Concluding Remarks on Personalized Management of Cardiovascular Diseases ........................................................... References.................................................................................... Personalized Therapy of Pulmonary Disorders...................... Introduction.................................................................................. Role of Genetic Ancestory in Lung Function.......................... Targeted Drug Delivery for Personalized Management of Pulmonary
Disorders.......................................................... Personalized Therapy of Asthma............................................ 274 275 275 275 276 277 279 279 279 284 285 286 286 286 287 288 289 289 291 293 303 308 310 311 311 312 312 313 313 314 317 317 317 317 318
Contents XX Personalized Management of Chronic Obstructive Pulmonary Disease...................................................................... Idiopathic Pulmonary Fibrosis................................................... Biomarkers of Interstitial Lung Disease.................................... References......................................................................................... 321 322 322 323 15 Personalized Therapy of Infectious Diseases............................ Introduction....................................................................................... Genetic Susceptibility to Infections.......................................... Personalized Use of Antibiotics................................................. Personalized Management of Sepsis.......................................... Personalized Management of Viral Infections..................... .. Management of HIV.................................................................... Personalized Treatment of Hepatitis В...................................... Personalized Treatment of Hepatitis C...................................... Personalized Management of COVID-19.................................. Personalized Management of Tuberculosis.............................. Personalized Management of Fungal Infections....................... References......................................................................................... 325 325 325 325 326 326 326 333 333 335 339 340 340 16 Personalized Management of Genetic Disorders.....................
Introduction....................................................................................... Molecular Diagnosis of Genetic Disorders.................................... Molecular Diagnostic Technologies............................................... Cytogenetics................................................................................ FISH with Probes to the Telomeres........................................... Single Copy FISH Probes........................................................... Comparative Genomic Hybridization........................................ Representational Oligonucleotide Microarray Analysis........... Diagnosis of Genomic Rearrangements by Multiplex PCR... Mutation Detection Technologies................................................... Biomarkers for Genetic Disorders................................................. Biomarkers for Down’s Syndrome............................................. Biomarkers for Muscular Dystrophy........................................ Biomarkers of Phenylketonuria................................................. Genetic Biomarkers for Psoriasis............................................... Biomarkers of Lysosomal Storage Disorders................................ Biomarkers of Niemann-Pick Disease...................................... Biomarkers of Mucopolysaccharidoses.................................... Biomarkers of LSD...................................................................... Biomarkers of Fabry’s Disease................................................... Sequencing in Genetic
Disorders................................................... DNA Sequencing for Prenatal Disorders.................................. Sequencing Genomes of the Newborn to Screen for Genetic Disorders....................................................................................... Study of Rare Variants in Pinpointing Disease-Causing Genes Personalized Cell and Gene Therapies of Genetic Disorders.... Personalized Stem Cell Transplant for Sickle Cell Anemia ... Hurler Syndrome.......................................................................... Personalized Gene Therapy of Duchenne Muscular Dystrophy..................................................................................... 343 343 343 344 344 344 344 345 345 345 346 347 347 347 348 348 349 349 350 351 351 352 353 353 354 356 356 356 357
XXI Contents 17 Personalized Treatment of Cystic Fibrosis.................................. Current Management of CF.................................................... Personalizing New Therapies for CF...................................... Gene Therapy and Pharmacogenomic Approach to CF.......... Personalized Treatment of Cystic Fibrosis.............................. Personalized Management of Prader-Willi Syndrome............ References.................................................................................... 358 359 359 359 359 360 361 Personalized Approaches to Immune Disorders.................... Introduction.......................... Immunological Tests in Personalized Medicine...................... Pharmacogenetics and Pharmacogenomics of Immunosuppression................................................................ Personalized Management of Patients with Lupus Erythematosus.............................................................................. Personalized Therapy of Rheumatoid Arthritis............................ Biomarkers and Diagnostics for Personalizing Therapy of Rheumatoid Arthritis................................................................ Genetics and Epigenetic Aspects of Rheumatoid Arthritis.... Personalization of COX-2 Inhibitor Therapy.......................... Personalized Biological Therapy of RA.................................. Personalization of Infliximab Therapy.................................... Personalized Therapy of RA Guided by Anti-citrullinated Protein
Antibodies.................................................................... Variations in the Effectiveness of Therapies for RA................ Personalized Approaches to Improve Organ Transplantation.... Personalization of Kidney Transplantation.............................. Personalization of Cardiac Transplantation............................ Prediction of Rejection for Personalizig Anti-rejection Treatment................................................................................ Personalized Immunosuppressant therapy in Organ Transplants.............................................................................. Role of Immunological Biomarkers in Monitoring Grafted Patients........................................................................ References.................................................................................... 363 363 364 18 Miscellaneous Areas of Personalized Medicine...................... Introduction.................................................................................. Personalized Management of Ophthalmic Disorders.................. Proteomics-Based Personalized Management of Uveitis........ Combining Cell and Gene Therapies for Retinal Disorders... Personalized Management of Skin Disorders.............................. Generic Testing for Personalized Skin Care............................ Management of Hair Loss Based on Genetic Testing.............. Personalized Urology.................................................................. Personalized Management of Obesity........................................
Basics of Obesity.................................................................... Genetics of Obesity as a Basis for Personalized Management............................................................................ Limitations of Personalized Approach to Management of Obesity................................................................................ 364 365 366 366 367 367 368 368 368 368 369 369 370 371 372 372 373 375 375 375 375 376 376 376 376 377 377 377 378 378
Contents XXII Personalized Management of Diabetes........................................... Biomarkers in the Management of Diabetes.............................. Closed Loop Control of typel DM............................................. Personalized Prediction of Postprandial Glycémie Response . Personalized Management of Monogenic Diabetes................. Selection from Multiple Options for Treatment of T2DM.... Stratification of Diabetes into 5 Subgroups and Personalized Medicine....................................................................................... Personalized Management of Gastrointestinal Disorders............. Role of Microbiome in Personalized Management of Gastrointestinal Disorders............................................................ Personalized Therapy of Inflammatory Bowel Disease........... Personalized Management of Lactose Intolerance................... Improved Matching of Blood Transfusion................................ Personalized Approaches to Addiction.......................................... Reversal of Cocaine-Evoked Synaptic Plasticity..................... Pharmacogenetics of Drug Addiction........................................ Genetic Polymorphism and Management of Alcoholism........ Personalized Therapy for Smoking Cessation.......................... Personalized Geriatrics.................................................................... Chronological Versus Biological Age........................................ Pharmacogenetics and Adverse Drug Reactions....................... Role of Biomarkers and
Ageotyping.......................................... Systems Pharmacology Approach to Disorders of Aging........ Personalized Pediatrics.................................................................... WGS for Personalized Management of Genetic Disorders in Critically Ill Infants...................................................................... Personalized Nephrology................................................................ Personalized Management of Chronic Kidney Disease........... Personalized Management of Renal Disease Associated with Hypertension................................................................................. Personalized Approach to Type I Primary Hyperoxaluria .... Personalized Gynecology................................................................ Female Sexual Dysfunction....................................................... Lower Urinary Tract Disorders in Women................................ Personalized Surgery........................................................................ Personalized Approaches to Miscellaneous Problems................. Personalized Treatment of Malaria............................................. Personalized Management of Osteoporosis.............................. Personalized Care of Trauma Patients...................................... Personalized Medical Care of Astronauts during Space Flights........................................................................................... Personalized Management of Motion Sickness....................... Personalized Treatment of Rare
Diseases.................................. Personalized Management of DNA Repair Disorders................. Personalized Preventive Medicine and Public Health................... Personalized Public Health......................................................... References......................................................................................... 378 379 379 379 380 380 380 381 381 382 382 383 383 383 384 384 385 387 387 387 387 388 388 388 388 388 390 391 391 392 392 392 393 393 394 395 395 396 396 399 399 400 400
Contents χχ։ϋ 19 Principles of Personalized Oncology......................................... Introduction.................................................................................. Epidemiology of Cancer.......................................................... Development of Personalized Therapy in Cancer.................... Molecular Biology of Cancer as Basis for Personalized Management............................................................................ Challenges of Cancer Classification........................................ Role of Staging in Personalized Management of Cancer........ Systems Biology of Cancer...................................................... Relationships of Technologies for Personalized Management of Cancer............................................................ Role of Molecular Diagnostics in the Management of Cancer... A Universal NGS-Based Oncology Test System.................... Analysis of RNA Splicing Events in Cancer.......................... Analysis of Chromosomal Alterations in Cancer Cells.......... Cancer Classification Using Microarrays................................ Cancer Gene Panel for Detection of Genetic Alterations........ Companion Diagnostics for Cancer........................................ Circulating Tumor Cells Isolation and Characterization........ Circulating Cell-Free DNA for Monitoring Personalized Cancer Therapy........................................................................ Detection of Loss of Heterozygosity...................................... Detection of Rare Mutations to Guide
Cancer Therapy.......... Diagnostics for Detection of Minimal Residual Disease........ DNA Repair Biomarkers.......................................................... DNA Sequencing for Prognosis of Cutaneous T Cell Lymphoma.............................................................................. Fluorescent In Situ Hybridization............................................ Gene Expression Profiling...................................................... Synthetic Lethality.................................................................. GPS Cancer Test...................................................................... Liquid Biopsy.......................................................................... Modulation of CYP450 Activity for Cancer Therapy.............. NanoFlares for Detection of CTCs.......................................... Pathway-Based Analysis of Cancer........................................ Quantum Dot-Based Test for DNA Méthylation.................... Role of Molecular Imaging in Personalized Therapy of Cancer.................................................................................. Unraveling the Genetic Code of Cancer.................................. Cancer Prognosis........................................................................ Personalized Cancer Prevention.................................................. Detection of Mutations for Cancer Risk Assessment and Prevention........................................................................ Impact of Biomarkers on Management of Cancer...................... Biomarker-Based
Assays for Predicting Response to Anticancer Therapeutics...................................................... HER-2/neu Oncogene as a Biomarker for Cancer.................. 403 403 403 403 403 408 409 409 410 410 411 412 412 412 413 413 413 414 415 415 416 416 416 417 417 419 419 420 420 421 421 422 422 425 425 426 426 427 427 427
Contents XXIV L-Asparaginase Treatment of Cancer Guided by a Biomarker................................................................................... miRNA Biomarkers for Personalized Management of Cancer....................................................................................... Oncogene GOLPH3 as a Cancer Biomarker............................ Predictive Biomarkers for Efficacy of Anticancer Therapy ... Sequencing to Discover Biomarkers to Personalize Cancer Treatment..................................................................................... Swiss Molecular Tumor Board for Individualized, Biomarker-Based Decisions....................................................... VeraTag™ Assay System for Cancer Biomarkers................... Determination of Response to Therapy........................................ Ex Vivo Testing of Tumor Biopsy for Chemotherapy Sensitivity..................................................................................... Genomic Approaches to Predict Response to Anticancer Agents........................................................................................... Non-genetic Factors for Variations in Response of Cancer Cells to Drugs.............................................................. Profiling of Cancer Therapy in Zebrafish Xenografts to Predict Response...................................................................... Proteomic Analysis of Tumor Biopsies to Predict Response to Treatment................................................................ Real-Time Apoptosis
Monitoring............................................... Serum Nucleosomes as Indicators of Sensitivity to Chemotherapy.............................................................................. Targeted Microbubbles to Tumors for Monitoring Anticancer Therapy............................................................................................ PET Imaging for Determining Response to Chemotherapy... Concluding Remarks About Predicting Response to Anticancer Therapy..................................................................... Molecular Diagnostics Combined with Cancer Therapeutics.... Aptamers for Combined Diagnosis and Therapeutics of Cancer.......................................................................................... Combining Diagnosis and Therapy of Metastatic Cancer .... Detection and Destrucdon of CTCs with Nanoparticles and X-Rays...................................................................................... Molecular Profiling of Cancer....................................................... Targeted Cancer Therapies................................................................. Targeting Angiogenesis in Cancer................................................ Targeting Glycoproteins on Cell Surface.................................. Targeting Pathways in Cancer..................................................... Targeted Personalized Anticancer Medicines in Clinical Use.............................................................................. Personalized Radiation Therapy.....................................................
Peptide Receptor Radionuclide Therapy....................................... Use of Radiation Sensitivity Biomarkers in Personalized Radiotherapy................................................................................... Use of Imaging to Monitor Radioimmunotherapy of Non-Hodgkin Lymphoma.......................................................... 428 428 429 429 429 430 430 430 431 431 434 434 434 435 435 435 436 437 437 437 438 439 439 439 439 440 440 440 440 442 442 443
xxv Contents Role of Nanobiotechnology in Personalized Management of Cancer........................................................................................... Selective Destruction of Cancer Cells While Sparing Normal Cells................................................................................. Tissue Systems Biology Approach to Personalized Management of Cancer................................................................ Role of Oncoproteomics in Personalized Therapy of Cancer.. . . Cancer Tissue Proteomics............................................................ Proteomics Technologies to Guide Targeted Drug Selection for Cancer.................................................................... Role of Metabolomics in Personalized Therapy of Cancer......... Manipulation of Tumor Metabolism for Personalizing Antitumor Effect.......................................................................... Role of Sequencing in Personalized Therapy of Cancer............... Pharmacogenomic-Based Chemotherapy....................................... Whole Genome Technology to Predict Drug Resistance......... Anticancer Drug Selection Based on Molecular Characteristics of Tumor.............................................................. Testing Microsatellite-Instability for Response to Chemotherapy............................................................................... Pharmacogenetics of Cancer Chemotherapy................................ CYP1A2....................................................................................... Thiopurine
Methyltransferase..................................................... Dihydropyrimidine Dehydrogenase........................................... UGT1A1 Test as Guide to Irinotecan Therapy.......................... Computers and Digital Technologies for Personalized Oncology............................................................................................ Artificial Intelligence in Personalized Management of Cancer....................................................................................... Computational Models of Kinetically Tailored Treatment.... Mathematical Modeling of Tumor Microenvironments........... Modeling Signaling Pathways to Reposition Anticancer Drugs.............................................................................................. Personalized Computational Oncology....................................... Therapy Resistance in Cancer.......................................................... Mechanism of Therapy Resistance in Cancer............................ Detection of Drug Resistance..................................................... Management of Drug Resistance in Cancer.............................. Personalized Therapy of Cancer Metastases.................................. Technologies for Analysis of CTCs........................................... Systemic Antitumor Effect of Localized Radiotherapy for Cancer Metastases.................................................................. Diagnosis of Cancer of an Unknown Primary.......................... Current Trends and Future of Personalized Oncology.................
Challenges for Developing Personalized Cancer Therapies... Personalizing Anticancer Drug Combinations.......................... Cancer Genome Atlas.................................................................. Cancer Moonshot........................................................................ COLTHERES Consortium......................................................... 443 444 445 445 445 446 447 447 448 449 449 449 450 450 451 451 452 452 453 453 453 454 454 454 455 455 456 457 459 460 461 462 462 463 464 465 465 466
Contents XXVI Computer and Imaging Technologies for Personalizing Cancer Treatment........................................................................ Genomic Cancer Care Alliance................................................... Integrated Genome-Wide Analysis of Cancer for Personalized Therapy.................................................................. International Cancer Genome Consortium................................ National Cancer Institute of US................................................. Precision Oncology Decision Support at MD Anderson Cancer Center............................................................................... PREDICT Consortium................................................................ Quebec Clinical Research Organization in Cancer................... The San Antonio 1000 Cancer Genomes Project..................... Design of Future Personalized Cancer Therapies.......................... Personalized Therapy of Cancer Based on Cancer Stem Cells............................................................................................. Role of CRISPR-Cas9 in Personalized Cancer Gene Therapy......................................................................................... Role of Epigenetics in Personalized Cancer Therapies........... References......................................................................................... 20 Personalized Immuno-Oncology................................................. Introduction.......................................................................................
Classification of Therapeutic Approaches in Immuno-Oncology.................................................................. Role of Biomarkers in Personalized Immuno-Oncology............. Organoids in Predicting Response to Immuno-Therapeutic Drugs................................................................................................. Role of Tumor-on-Chips in Immuno-Oncology........................ Role of Molecular Diagnostics and Sequencing in Immuno-Oncology...................................................................... Genomic Testing.......................................................................... Gene Expression Signatures....................................................... Integration of Technologies for Personalized Immuno-Oncology.......................................................................... Factors that Drive the Development of Personalized Immunotherapy for Cancer......................................................... Computational Methods for Personalized Immuno-Oncology...................................................................... Prediction of Response to Anti-PD-l/PD-Ll Therapy in Cancer........................................................................................... Monoclonal Antibodies for Personalized Management of Cancer............................................................................................... Targeted MAb-Based Immune therapy of Cancer................... MAbs for Immune Activation..................................................... Immunotherapy of Dormant
Cancer.......................................... Antibody-Drug Conjugates for Personalized Therapy of Cancer....................................................................................... Combining Diagnostics with Therapeutics Based on MAbs....................................................................................... Immune Checkpoint Inhibitors for Cancer.................................... 467 467 467 468 469 471 471 471 472 472 472 473 473 475 479 479 479 479 481 481 481 481 482 482 483 483 484 484 485 486 486 487 487 488
Contents xxvii Checkpoint Inhibitors Blocking PD-1 or PD-Ll....................... 488 Antibody Blocking the Cytotoxic T-Lymphocyte-Associated Protein 4........................................... 489 Checkpoint Inhibitors Other than Anti-PD-Ll........................... 489 Personalizing Immune Checkpoint Inhibitor Therapy............ 490 Cell-Based Immune Therapies....................................................... 490 Treatments for Cancer by Ex Vivo mobilization of Immune Cells......................................................................... 490 Granulocytes as Anticancer Agents............................................. 491 Neutrophil Granulocytes in MAb-Based Immunotherapy of Cancer.................................................................................. 491 Adoptive Cell Transfer............................................................ 491 Chimeric Antigen Receptor T Cells........................................... 492 Cytokines....................................................................................... 492 Personalized Cancer Vaccines......................................................... 493 Antigen-Specific Vaccines......................................................... 493 Tumor-Derived Vaccines............................................................. 494 Patient-Specific Cell-Based Vaccines......................................... 496 Adoptive Cell Therapy............................................................... 498 Personalized Peptide Cancer Vaccines....................................... 500 Targeting Core
mutations in Cancer........................................ 501 Current Status and Future of Personalized Cancer Vaccines .. 501 Cytokines as Vaccine Adjuvants.............................................. 501 Limitations of Cancer Vaccination............................................. 502 Role of neoantigens in Personalizing Cancer Vaccines.......... 503 Immunogene Therapy..................................................................... 503 Delivery of Cancer Immunotherapy............................................... 503 Nanoparticles for Delivery of Immunotherapy plus Photodynamic Therapy....................................................................................... 504 Synthetic Bacteria for Local Tumor Delivery of Checkpoint Blockade Nanobodies................................................................. 504 Transdermal Cold Atmospheric Plasma Mediated ICI Therapy................................................................................. 504 Combination of Immunotherapies for Cancer............................... 505 Concluding Remarks and Future of Personalized Immuno-Oncology......................................................................... 506 References....................................................................................... 506 21 Personalized Management of Cancers of Various Organs/Systems............................................................................. 509 Introduction..................................................................................... 509 Personalized Management of Bladder
Cancer........................... 509 Personalized Management of Brain Tumors............................... 511 Personalized Management of Breast Cancer............................. 524 Personalized Management of Ovarian Cancer........................... 546 Personalized Management of Head and Neck Cancer............ 553 Personalized Management of Hematological Malignancies... 554 Personalized Management of Gastrointestinal Tumors.......... 566 Personalized Management of Colorectal Cancer....................... 568 Personalized Management of Liver Cancer............................... 575
Contents xxviii 22 Personalized Management of Lung Cancer.............................. Personalized Management of Malignant Melanoma............... Personalized Management of Endocrine Tumors..................... Personalized Management of Osteosarcoma............................ Personalized Management of Pancreatic Cancer..................... Personlized Management of Prostate Cancer............................ Personalized Management of Thyroid Cancer.......................... References......................................................................................... 577 585 587 590 591 592 596 596 Development of Personalized Medicine...................................... Introduction....................................................................................... Drug Discovery and Development................................................. Repositioning of Drugs for Personalized Medicine................. Discovery of Personalized Medicines........................................ Personalized Drug Delivery....................................................... Production and Distribution of Personalized Medicines........... Role of Molecular Imaging in Personalized Medicine............. Role of Genetic Banking Systems and Databases........................ Role of Biobanks in Development of Personalized Medicine . UK Biobank................................................................................ Biobanking and Development of Personalized Medicine in EU............................................................................ CARTaGENE for
Biobanks in Canada...................................... Personalized Medicine Based on PhysioGenomics™ Technology.................................................................................. Role of Bioinformatics in Development of Personalized Medicine........................................................................................... Biosimulation Techniques for Developing Personalized Medicine....................................................................................... Biosensing and Wearable Devices for Monitoring of Health.. Clinical Decision Support Systems............................................. Digitalized Medicine.................................................................... Genomic Data Analysis................................................................ Integration of Omics Data by Deep Learning............................ Health Information Management............................................... Electronic Health Records......................................................... Personalized Prognosis of Disease............................................. Personalized Approach to Clinical Trials...................................... Adaptive Clinical Trials............................................................. Bayesian Approach in Biomarker-Based Clinical Trials........ Clinical Trials of Therapeutics and Companion Diagnostics .. Clinical Trials on Selected Subpopulations of Patients........... Clinical Trials Networks............................................................. Creative Clinical Trial
Design..................................................... Individualzing Risks and Benefits in Clinical Trials................. References......................................................................................... 603 603 603 603 604 604 604 605 608 608 609 609 609 610 610 612 612 613 613 613 614 614 614 618 618 619 620 621 622 622 622 623 623
Contents XXIX 23 24 Players in the Development of Personalized Medicine........... Introduction....................................................................................... Personalized Medicine Coalition............................................... Role of Pharmaceutical Industry..................................................... Role of Biotechnology Companies................................................. Role of Life Sciences Industries..................................................... Role of Biomedical Engineering in Wearable Devices for Personalized Healthcare....................................................... Role of the Clinical Laboratories................................................... Role of the US Government in Personalized Medicine............... Precision Medicine Initiative..................................................... Department of Health and Human Services and Personalized Medicine....................................................................................... Agency for Healthcare Research and Quality............................ Comparative Effectiveness Research........................................ Role of the US Government Agencies in Personalized Medicine....................................................................................... Role of Academic Institutions and Organizations in the US .. Role of Academic Collaborations with Companies................. Role of Healthcare Organizations............................................... Role of the Medical
Profession................................................... Role of Patients............................................................................. Advantages of Personalized Medicine for Players........................ References......................................................................................... 625 625 625 625 627 627 Global Scope of Personalized Medicine.................................... Global Alliance for Genomics and Health.................................... Precision Medicine Project of World Economic Forum............... Personalized Medicine in Canada................................................... Personalized Medicine at Ontario Institute for Cancer Research....................................................................................... Personalized Medicine Partnership for Cancer in Quebec .... Quebec Center of Excellence in Personalized Medicine......... Personalized Medicine in the EU................................................... European Personalized Medicine Diagnostics Association . .. European Ubiquitous Pharmacogenomics Project................... UK National Health Service and Medical Genetics..................... UK’s 100,000 Genomes Project................................................. UK’s Precision Medicine Catapult............................................. Personalized Medicine in France............................................... Personalized Medicine in Germany............................................... Personalized Medicine in Israel.....................................................
Personalized Medicine in Japan..................................................... Biobanks in Japan........................................................................ Companion Diagnostics in Japan............................................... Cost-Effectiveness of Personalized Medicine in Japan........... 661 661 661 662 628 628 629 630 632 633 634 635 639 652 652 653 654 658 659 662 664 664 664 665 665 665 666 666 666 667 667 668 668 668 669
Contents xxx 25 26 27 Genetic Testing in Japan.............................................................. Initiative on Rare and Undiagnosed Diseases............................ Personalized Medicine in the Developing Countries................... Personalized Medicine in the Middle East.................................... Personalized Medicine in China..................................................... Personalized Medicine in India....................................................... Personalized Medicine in Africa..................................................... 669 669 670 670 671 671 671 Ethical Issues in Personalized Medicine.................................... Introduction to Ethical Issues......................................................... Ethical Issues of Pharmacogenetics............................................... Ethical Aspects of Genetic Information........................................ Ethical Issues of Whole Genome Analysis................................ Privacy Issues in Personalized Medicine.................................. Genetic Information Nondiscrimination Act in theUS............ UNESCO and Ethical Aspects of Personalized Medicine .... Genotype-Specific Clinical Trials................................................... Ethical Issues in Use of Digital Technologies for Personalized Medicine........................................................................................... Social Issues in Personalized Medicine........................................ Disparities in Healthcare Among Various Populations.................
Race and Personalized Medicine................................................... Genetic Testing and Concerns About Disparities in Healthcare.. Pharmacogenomics/Pharmacogenetics in Racial/Ethnic Populations....................................................................................... Racial and Ethnic Differences in Disease Epidemiology and Response to Therapy................................................................ Race and Cancer.......................................................................... Race and Alzheimer Disease....................................................... Race and Coronary Heart Disease............................................. Race and Inflammatory Bowel Disease.................................... Tackling Racial Issues and Improving Access to Genomic Medicine........................................................................................... References......................................................................................... 673 673 673 674 674 674 675 675 676 Legal Regulatory Aspects of Personalized Medicine........... Legal Aspects of Personalized Medicine...................................... Gene Patents and Personalized Medicine.................................. Regulatory Aspects.......................................................................... FDA and Personalized Medicine............................................... FDA and Molecular Diagnostics in Relation to Personalized Medicine....................................................................................... Regulatory
Aspects of Pharmacogenetics.................................. Regulation of Direct-to-Consumer Genetic Testing................. FDA and Pharmacogenomics..................................................... FDA and Predictive Medicine..................................................... References......................................................................................... 683 683 683 684 684 Economics of Personalized Medicine........................................ Introduction....................................................................................... Personalized Medicine and Drug Markets................................ 701 701 701 676 677 677 677 678 678 679 680 680 680 680 681 681 685 691 692 695 699 700
Contents XXXI Perceived Financial Concerns.................................................. Personalized Medicine and Orphan Drug Syndrome.............. Commercial Aspects of Pharmacogenomics................................ Cost of DNA Testing................................................................ Cost of Sequencing the Human Genome................................ Cost of Genotyping.................................................................. Cost of Pharmacogenomics-Based Clinical Trials.................. Business Development of Pharmacogenomic Companies .... Cost of Personalized Healthcare.................................................. The Rising Healthcare Costs in the US.................................... Genetic Testing and Cost of Healthcare.................................. Personalized Medicine for Reducing Cost of Care of Cancer.................................................................................. Reducing Healthcare Costs by Combining Diagnostics with Therapeutics.................................................................... Reducing the Cost of Treatment of Acte Myeloid Leukemia.. Cost-Effectiveness of Personalized Medicine.............................. Early Cost-Effectiveness Analysis of New Personalized Medicine Technologies............................................................ Cost-Effectiveness of Pharmacogenetic Testing...................... Cost-Effectiveness of CYP Genotyping-Based Pharmacotherapy...................................................................... Cost Effectiveness of HIV Genotyping in
Treatment of AIDS.................................................................................... Cost-Effectiveness of Warfarin Pharmacogenomics................ Overall Economic Impact of Personalized Medicine on Healthcare............................................................................ References.................................................................................... 28 Future of Personalized Medicine.............................................. Introduction.................................................................................. Personal Genome Project........................................................ Translational Science and Personalized Medicine.................. Personalized Predictive Medicine............................................ Connected Health and Personalized Medicine........................ Challenges and Opportunities for Personalized Medicine .... Medicine in the Year 2025 .......................................................... Concluding Remarks About the Future of Personalized Medicine...................................................................................... References.................................................................................... Index 701 702 702 702 702 704 705 705 705 705 706 706 708 708 709 709 709 710 710 711 711 711 713 713 713 715 717 717 718 722 723 724 725
Kewal К. Jain Textbook of Personalized Medicine Third Edition This book is for personalized medicine as a prescription of specific treatments and therapeutics best suited for an individual and considersgenetic as well as environmental factors that influence responses to therapy. Best approaches are described for integration of all available technologies for optimizing the therapy of individual patients. This comprehensive third edition covers the latest advances in personalized medicine and several chapters are devoted to various specialties, particular}՛ cancer which is the largest area of application. The book discusses the development of personalized medicine and various playersin it such as companies, academic institutions, the government, and the public as the consumer of healthcare. Additionally, the roles of bioinformatics, electronic health records, and digital technologies for personalized medicine are discussed. Textbook of Personalized Medicine, 3rd Edition serves as a convenient source of information for students at many levels and in a wide range of fields, including physicians, scientists, and decision makers in the biopharmaceutical and healthcare industries.
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Contents 1 Basic Aspects. Definition of Personalized Medicine. Personalized Medicine as 1 OP Medicine. History of Medical Concepts Relevant to Personalized Medicine. Evolution of Modern Personalized Medicine. Molecular Biological Basis of Personalized Medicine. The Human Genome. Chromosomes. Genes. Genetic Variations in the Human Genome. Mitochondrial tRNA and Personalized Medicine. Molecular Pathology. Basics Technologies for Developing Personalized Medicine. Definitions of Technologies Relevant to Personalized Medicine. Problems with the ICH Definitions of Pharmacogenomics and Pharmacogenetics. Omics’ and Personalized Medicine. Relationship of Various Technologies to Personalized Medicine. Conventional Medicine
Versus Personalized Medicine. Personalized Medicine and Evidence-Based Medicine. Role of Genetics in Future Approaches to Healthcare. Genetic Medicine. Human Disease and Genes. Genetic and Environmental Interactions in Etiology of Human Diseases. Role of Genetics in Development of Personalized Medicines. Role of Epigenetics in Personalized Medicine. Role of Systems Biology in Personalized Medicine. Systems Pharmacology. Systems Medicine. Synthetic Biology and Development of Personalized Medicines. Personalized Digital Medicine. Artificial Intelligence in Personalized Medicine. 1 1 3 3 5 5 5 7 7 8 16 16 17 17 18 18 18 18 19 20 20 20 21 21 23 24 25 25 27 28 28 xi
Contents xii 2 Machine Learning and Personalized Medicine. Algorithms Based on Machine Learning. Bioelectronics and Personalized Medicine. A Personalized Approach to Environmental Factors in Disease. Role of Animal Models in Development of Personalized Medicine. Animal Models for Supplementing Research on Human Genomes. Mouse Models for Personalized Medicine. Promise and Limitations of Animal Models for Personalized Medicine. Role of Pets with Naturally Occuring Diseases. Reclassification of Diseases. Translational Science and Personalized Medicine. Genome to Phenome Translation. Personalization of Multimodal Therapies. Applications of Personalized Medicine in Various Therapeutic Areas. References. 29 29 29 Molecular Diagnostics in Personalized
Medicine. Introduction. Molecular Diagnostic Technologies. DirectLinear™ Analysis. Denaturing High-Performance Liquid Chromatography. Multiplex Allele-Specific Diagnostic Assay. Restriction Fragment Length Polymorphism (RFLP). Real-Time PCR for Detection of CNVs. Non-PCR Methods. DNA Sequencing. Emerging Sequencing Technologies. Ion Torrent’s Sequencing Technology. Biochips and Microarrays. Role of Biochip/Microarray Technology in Personalized Medicine. Applications of Biochip/Microarray Technology in Personalized Medicine. Standardizing the Microarrays. Biochip Technologies. Microfluidics. Electronic Detection of Nucleic Acids on Microarrays. Strand
Displacement Amplification on a Biochip. Rolling Circle Amplification on DNA Microarrays. Universal DNA Microarray Combining PCR and Ligase Detection Reaction. Protein Biochips. SNP Genotyping. Genotyping and Haplotyping. Technologies for SNP Analysis. 39 39 39 41 41 41 41 42 42 43 44 48 60 30 30 31 31 32 32 33 34 34 34 34 35 60 61 61 62 63 65 66 66 66 67 70 71 75
xiii Contents ay-Based Detection of SNPs. Electrochemical DNA Probes. . ■. · Laboratory Multiple Analyte Profile. PCR-CTPP (Confronting Two-Pair Primers). TaqMan Real-Time PCR. Locked Nucleic Acid. Molecular Inversion Probe Based Assays. Pyrosequencing. Smart Amplification Process Version 2. Zinc Finger Proteins. Mitochondrial SNPs. Limitations of SNP in Genetic Testing. Concluding Remarks on SNP Genotyping. Impact of SNPs on Personalized Medicine. Detection of Copy Number Variations. CNVer Algorithm for CNV Detection. CNVnator for Discovery of CNVs and Genotyping. Study of Rare Variants in Pinpointing Disease-Causing Genes. Optical Mapping. Proteomics in Molecular
Diagnosis. Layered Gene Scanning. Comparison of Proteomic and Genomic Approaches in Personalized Medicine. Role of Biosensors in Personalized Medicine. Gene Expression Profiling. DNA Microarrays. Analysis of Single-Cell Gene Expression. Gene Expression Profiling Based on Alternative RNA Splicing. Whole Genome Expression Array. Tangerine™ Expression Profiling. Gene Expression Analysis on Biopsy Samples. Profiling Gene Expression Patterns of White Blood Cells . Serial Analysis of Gene Expression (SAGE). Multiplexed Molecular Profiling. Gene Expression Analysis Using Competitive PCR and MALDI TOF MS. Monitoring In Vivo Gene Expression by Molecular Imaging. Molecular Imaging and Personalized Medicine. Combination of Diagnostics and Therapeutics. Use of Molecular Diagnostics for Stratification in
Clinical Trials. Companion Diagnostics. Companies Involved in Companion Diagnostics. Point-of-Care Diagnosis. Point-of-Care Diagnosis of Infections. Advantages Versus Disadvantages of Point-of-Care Diagnosis. 75 77 77 77 78 78 78 78 79 79 79 80 80 81 81 81 81 82 82 83 83 84 84 85 86 86 87 88 88 88 89 89 90 90 91 91 91 92 92 92 93 94 95
Contents XIV Future of Point-of-Care Diagnosis. Genetic Testing for Disease Predisposition. Preventive Genetics by Early Diagnosis of Mitochondrial Diseases. Direct-to-Consumer Genetic Services. Personalized Polygenic Risk Scores. Role of Diagnostics in Integrated Healthcare. Concept of Integrated Healthcare. Components of Integrated Healthcare. Advantages and Limitations of Integrated Healthcare. Commercially Available Systems for Integrated Healthcare . Future of Molecular Diagnostics in Personalized Medicine. References. 3 4 95 96 96 96 97 97 97 98 99 100 100 100 Role of Biomarkers in Personalized Medicine. Introduction. Definitions. Biomarker as a Response to Therapeutic Intervention. Pharmacokinetic/Pharmacodynamics Biomarkers. Predictive В iomarkers. Biomarkers of Drug
Safety. Applications of Biomarkers. Diagnostic Applications of Biomarkers. Applications of Biomarkers for Targeted Therapies. Proteomic Strategies for Biomarker Identification. Proteomic Technologies for Detection of Biomarkers in Body Fluids. Protein Patterns. Biomarkers for Diagnostics. Biomarkers for Drug Development. Role of Biomarkers in Development of Personalized Drugs . Bioinformatics to Sort Biomarker Data for Personalized Medicine. Use of Bayesian Approach in Biomarker-Based Clinical Trials. Biomarkers for Monitoring Response to Therapy. Drug Rescue by Biomarker-Based Personalized Medicine. Biobanking, Biomarkers and Personalized Medicine in EU . Biomarkers Consortium Personalized Medicine. Future Role of Biomarkers in Personalized Medicine. References. 103 103 103 104 104 104 105 105 105 106 107
Pharmacogenetics. Basics of Pharmacogenetics. Role of Molecular Diagnostics in Pharmacogenetics. Role of Pharmacogenetics in Pharmaceutical Industry. Study of the Drug Metabolism and Pharmacological Effects. Causes of Variations in Drug Metabolism. Enzymes Relevant to Drug Metabolism. Pharmacogenetics of Phase I Metabolism. 115 115 116 116 117 118 118 119 107 108 108 108 108 109 109 110 Ill Ill 112 112 113
Contents XV 5 Pharmacogenetics of Phase II Metabolism. Measurement of CYP Isoforms. Polymorphism of Drug Transporters. Genetic Variation in Drug Targets. Effect of Genetic Polymorphisms on Disease Response to Drugs. Ethnic Differences in Drug Metabolism. Gender Differences in Pharmacogenetics. Role of Pharmacogenetics in Drug Safety. Therapeutic Drug Monitoring, Phenotyping, and Genotyping. Phenomics. Molecular Toxicology in Relation to Personalized Medicines. Pharmacogenetics in Clinical Trials. Postmarketing Pharmacogenetics. Clinical Implications of Pharmacogenetics. HLA Alleles Associated with Lumiracoxib-Related Liver Injury. Pharmacogenomic Biomarker Information in Drug Labels . Pharmacogenetic Basis of Thiopurine Toxicity. Tranilast-Induced Hyperbilirubinemia Due to Gene Polymorphism. Standardized Terminology for Clinical Pharmacogenetic Test
Results. Use of Pharmacogenetics in Personalized Medicine. Linking Pharmacogenetics with Pharmacovigilance. Recommendations for the Clinical Use of Pharmacogenetics . Limitations of Pharmacogenetics. Pharmacoepigenomics Versus Pharmacogenetics in Drug Safety. Future Role of Pharmacogenetics in Personalized Medicine . References. 123 124 125 125 Pharmacogenomics. Introduction. Basics of Pharmacogenomics. Pharmacogenomics and Drug Discovery. Preclinical Prediction of Drug Efficacy. Role of Pharmacogenomics in Drug Discovery and Drug Delivery. Next Generation Sequencing and Pharmacogenomics. Pharmacogenomics and Clinical Trials. Impact of Genetic Profiling on Clinical Studies. Limitations of the Pharmacogenomic-Based Clinical Trials . Pharmacogenomic Aspects of Major Therapeutic Areas.
Oncogenomics. Cardiogenomics. Neuropharmacogenomics. Current State and Future of Pharmacogenomics. References. 153 153 153 154 156 125 126 127 128 136 138 139 140 141 141 141 142 146 147 147 147 149 150 150 151 151 152 156 156 156 157 158 159 159 161 162 165 166
Contents XVI 6 7 8 Role of Pharmacoproteomics. Basics of Proteomics. Proteomic Approaches to the Study of Pathophysiology of Diseases. Single Cell Proteomics for Personalized Medicine. Diseases Due to Misfolding of Proteins. Therapies for Protein Misfolding. Significance of Mitochondrial Proteome in Human Disease . Proteomic Technologies for Drug Discovery and Development. Proteins and Drug Action. Role of Reverse-Phase Protein Microarray in Drug Discovery. Role of Proteomics in Clinical Drug Safety. Toxicoproteomics. Role of Protein Biochips in Personalized Medicine. Role of Nanoproteomics in Personalized Medicine. Applications of Pharmacoproteomics in Personalized Medicine. Proteomic Biomarkers and Personalized Medicine. Role of Proteomics-Based Molecular Diagnostics in Personalized Medicine.
References. 167 167 168 169 169 169 170 171 171 171 171 172 173 173 174 174 175 175 Role of Metabolomics in Personalized Medicine. Metabolomics and Metabonomics. Metabolome Database. Metabolomics Bridges the Gap Between Genotype and Phenotype. Metabolomic Technologies. Lipid Profiling. Applications Relevant to Personalized Medicine. Pharmacometabolomics/Pharmacometabonomics. Metabonomic Technologies for Toxicology Studies. Metabolomics and Biomarkers. Metabonomics/Metabolomics and Personalized Nutrition. Metabolomics for Personalized Medicine. References. 177 177 177 Non-genomic Aspects of Personalized Medicine. Introduction. Non-genomic Factors in Response to Drugs. Personalized Medicine Based on Circadian Rhythms. Cytomics as a Basis for Personalized
Medicine. Intestinal Microflora and Personalized Medicine. Gut Microbiome Compared to Human Genome. Metabolic Interactions of the Host and the Intestinal Microflora. Role of Drug Delivery in Personalized Medicine. Role of Nanobiotechnology in Personalized Medicine. Role of Nanobiotechnology in Molecular Diagnostics. 185 185 185 186 187 187 187 178 178 179 180 180 180 181 182 183 183 188 188 189 189
Contents xvii Nanobiotechnology for Therapeutics Design and Monitoring. Nanobiotechnology for Therapeutic Applications. References. 190 191 193 9 Personalized Biological Therapies. Introduction. Recombinant Human Proteins. Therapeutic Monoclonal Antibodies. Cell Therapy. Autologous Tissue and Cell Transplants. Stem Cells. Cloning and Personalized Cell Therapy. Use of Stem Cells for Drug Testing. Gene Therapy. Gene Editing by CRISPR/Cas9 System. Personalized Gene Therapy for Cancer. Personalized Vaccines. Personalized Vaccines for Viral Diseases. Personalized Cancer Vaccines. Antisense
Therapy. RNA Interference. MicroRNAs. References. 195 195 195 195 196 196 196 197 197 198 198 199 199 199 200 200 200 201 201 10 Personalized Complementary Alternative Therapies. Introduction. Ayurveda as a Personalized Healthcare System. Taditional Chinese Medicine. Personalized Hyperbaric Oxygen Therapy. Personalized Nutrition. Nutrigenomics. Nutrigenetics and Personalized Medicine. Personalized Diet Prescription. Role of Systems Medicine in Personalized Nutrition. Personalized Physical Exercise. Aerobic Exercise Response Variations in Individuals. Exercise-Induced Muscle Hypertrophy and Strength Variations. Personalized Exercise for Prevention of Functional Decline in the
Elderly. References. 203 203 203 203 204 205 206 208 209 210 211 211 Personalized Therapy of Neurological Disorders. Introduction. Individuality of the Human Brain as a Basis of Personalized Neurology. Gender Differences in Neurological Disorders. Measuring Brain Health across Life Span. AI for Personalized Neurology. 213 213 11 211 212 212 213 214 214 215
Contents xviii 12 Personalized Management of Alzheimer’s Disease. Personalized Management of Parkinson’s Disease. Personalized Management of Huntington Disease. Personalized Management of Amyotrophic Lateral Sclerosis. Personalized Management of Epilepsy. Personalized Management of Migraine. Personalized Management of Intracranial Aneurysms. Personalized Management of Stroke. Personalized Treatment of Multiple Sclerosis. Personalized Management of Traumatic Brain Injury. Personalized Management of Myasthenia Gravis. Personalized Management of Tinnitus. Personalized Management of Pain. Personalized Management of Sleep Disorders. Future of Personalized Neurology. References. 215 217 221 Personalized Therapy of Psychiatric Disorders. Introduction. Role of Amygdala in Personalized Psychiatry. Gene Polymorphisms as Basis of Personalized Approach to Psychiatric
Disorders. Psychopharmacogenetics/Psychopharmacodynamics. Serotonin Genes. Calcium Channel Gene. Dopamine Receptor Genes. COMT Genotype and Response to Amphetamine. Methylenetetrahydrofolate Reductase. Genetic Loci Associated with Risk of Major Depressive Disorder. Role of Gene Mutations in ADHD. Genotype and Response to Methylphenidate in Children with ADHD. GeneSight Tests for Individualized Therapy of Psychiatric Disorders. Personalized Antipsychotic Therapy for Schizophrenia. Pharmacogenetics for Personalizing Antipsychotic Therapy . Patient-Derived Stem Cells for Personalizing Drugs for Schizophrenia. Personalized Therapy of Bipolar Disorder. Personalized Antidepressant Therapy. Pharmacogenetics/Pharmacogenomics of Antidepressant
Therapy. Biomarkers of Response to Antidepressant Treatment. EEG Biomarkers for Predicting Safety and Efficacy of Antidepressants. GeneSight Pharmacogenomic Test. Individualization of SSRI Treatment. 263 263 263 222 222 231 233 234 241 247 249 249 250 256 258 258 263 264 264 264 265 265 265 266 266 266 266 267 267 269 269 269 270 271 271 272 273
XIX Contents Role of Protein sFRP3 in Predicting Response to Antidepressants. Treatment of Depression Guided by Pharmacogenetics. Vilazodone with a Test for Personalized Treatment of Depression. Personalized Management of Alcohol Use Disorder. Personalized Management of Autism Spectrum Disorders. References. 13 14 Personalized Therapy of Cardiovascular Disorders. Cardiovascular Disorders. Role of Diagnostics in Personalized Management of Cardiovascular Disease. Assessing Patients with Coronary Heart Disease. Assessing Coronary Artery Disease for Percutaneous Coronary Interventions. Companion Diagnostics for Therapy of Cardiovascular Disorders. Biomarkers and Personalized Management of Cardiovascular Disorders. Pharmacogenomics of Cardiovascular Disorders. Nanotechnology-Based Personalized Therapy of Cardiovascular Diseases. Personalized Management of Chronic Myocardial Ischemia.
Personalized Management of Myocardial Infarction. Management of Heart Failure. Management of Atrial Fibrillation. Management of Hypertension. Personalized Lipid-Lowering Therapies. Thrombotic Disorders. Personalized Management of Aortic Aneurysms. Clinical Trials of Personalized Therapy of Cardiovascular Diseases. Project euHeart for Personalized Management of Heart Disease. Modification of Life Style Factors in Management of Cardiovascular Disorders. Multimorbidity in Patients with Cardiovascular Disease. Systems Biology Approach to Personalized Cardiology. Concluding Remarks on Personalized Management of Cardiovascular Diseases . References. Personalized Therapy of Pulmonary Disorders. Introduction. Role of Genetic Ancestory in Lung Function. Targeted Drug Delivery for Personalized Management of Pulmonary
Disorders. Personalized Therapy of Asthma. 274 275 275 275 276 277 279 279 279 284 285 286 286 286 287 288 289 289 291 293 303 308 310 311 311 312 312 313 313 314 317 317 317 317 318
Contents XX Personalized Management of Chronic Obstructive Pulmonary Disease. Idiopathic Pulmonary Fibrosis. Biomarkers of Interstitial Lung Disease. References. 321 322 322 323 15 Personalized Therapy of Infectious Diseases. Introduction. Genetic Susceptibility to Infections. Personalized Use of Antibiotics. Personalized Management of Sepsis. Personalized Management of Viral Infections. . Management of HIV. Personalized Treatment of Hepatitis В. Personalized Treatment of Hepatitis C. Personalized Management of COVID-19. Personalized Management of Tuberculosis. Personalized Management of Fungal Infections. References. 325 325 325 325 326 326 326 333 333 335 339 340 340 16 Personalized Management of Genetic Disorders.
Introduction. Molecular Diagnosis of Genetic Disorders. Molecular Diagnostic Technologies. Cytogenetics. FISH with Probes to the Telomeres. Single Copy FISH Probes. Comparative Genomic Hybridization. Representational Oligonucleotide Microarray Analysis. Diagnosis of Genomic Rearrangements by Multiplex PCR. Mutation Detection Technologies. Biomarkers for Genetic Disorders. Biomarkers for Down’s Syndrome. Biomarkers for Muscular Dystrophy. Biomarkers of Phenylketonuria. Genetic Biomarkers for Psoriasis. Biomarkers of Lysosomal Storage Disorders. Biomarkers of Niemann-Pick Disease. Biomarkers of Mucopolysaccharidoses. Biomarkers of LSD. Biomarkers of Fabry’s Disease. Sequencing in Genetic
Disorders. DNA Sequencing for Prenatal Disorders. Sequencing Genomes of the Newborn to Screen for Genetic Disorders. Study of Rare Variants in Pinpointing Disease-Causing Genes Personalized Cell and Gene Therapies of Genetic Disorders. Personalized Stem Cell Transplant for Sickle Cell Anemia . Hurler Syndrome. Personalized Gene Therapy of Duchenne Muscular Dystrophy. 343 343 343 344 344 344 344 345 345 345 346 347 347 347 348 348 349 349 350 351 351 352 353 353 354 356 356 356 357
XXI Contents 17 Personalized Treatment of Cystic Fibrosis. Current Management of CF. Personalizing New Therapies for CF. Gene Therapy and Pharmacogenomic Approach to CF. Personalized Treatment of Cystic Fibrosis. Personalized Management of Prader-Willi Syndrome. References. 358 359 359 359 359 360 361 Personalized Approaches to Immune Disorders. Introduction. Immunological Tests in Personalized Medicine. Pharmacogenetics and Pharmacogenomics of Immunosuppression. Personalized Management of Patients with Lupus Erythematosus. Personalized Therapy of Rheumatoid Arthritis. Biomarkers and Diagnostics for Personalizing Therapy of Rheumatoid Arthritis. Genetics and Epigenetic Aspects of Rheumatoid Arthritis. Personalization of COX-2 Inhibitor Therapy. Personalized Biological Therapy of RA. Personalization of Infliximab Therapy. Personalized Therapy of RA Guided by Anti-citrullinated Protein
Antibodies. Variations in the Effectiveness of Therapies for RA. Personalized Approaches to Improve Organ Transplantation. Personalization of Kidney Transplantation. Personalization of Cardiac Transplantation. Prediction of Rejection for Personalizig Anti-rejection Treatment. Personalized Immunosuppressant therapy in Organ Transplants. Role of Immunological Biomarkers in Monitoring Grafted Patients. References. 363 363 364 18 Miscellaneous Areas of Personalized Medicine. Introduction. Personalized Management of Ophthalmic Disorders. Proteomics-Based Personalized Management of Uveitis. Combining Cell and Gene Therapies for Retinal Disorders. Personalized Management of Skin Disorders. Generic Testing for Personalized Skin Care. Management of Hair Loss Based on Genetic Testing. Personalized Urology. Personalized Management of Obesity.
Basics of Obesity. Genetics of Obesity as a Basis for Personalized Management. Limitations of Personalized Approach to Management of Obesity. 364 365 366 366 367 367 368 368 368 368 369 369 370 371 372 372 373 375 375 375 375 376 376 376 376 377 377 377 378 378
Contents XXII Personalized Management of Diabetes. Biomarkers in the Management of Diabetes. Closed Loop Control of typel DM. Personalized Prediction of Postprandial Glycémie Response . Personalized Management of Monogenic Diabetes. Selection from Multiple Options for Treatment of T2DM. Stratification of Diabetes into 5 Subgroups and Personalized Medicine. Personalized Management of Gastrointestinal Disorders. Role of Microbiome in Personalized Management of Gastrointestinal Disorders. Personalized Therapy of Inflammatory Bowel Disease. Personalized Management of Lactose Intolerance. Improved Matching of Blood Transfusion. Personalized Approaches to Addiction. Reversal of Cocaine-Evoked Synaptic Plasticity. Pharmacogenetics of Drug Addiction. Genetic Polymorphism and Management of Alcoholism. Personalized Therapy for Smoking Cessation. Personalized Geriatrics. Chronological Versus Biological Age. Pharmacogenetics and Adverse Drug Reactions. Role of Biomarkers and
Ageotyping. Systems Pharmacology Approach to Disorders of Aging. Personalized Pediatrics. WGS for Personalized Management of Genetic Disorders in Critically Ill Infants. Personalized Nephrology. Personalized Management of Chronic Kidney Disease. Personalized Management of Renal Disease Associated with Hypertension. Personalized Approach to Type I Primary Hyperoxaluria . Personalized Gynecology. Female Sexual Dysfunction. Lower Urinary Tract Disorders in Women. Personalized Surgery. Personalized Approaches to Miscellaneous Problems. Personalized Treatment of Malaria. Personalized Management of Osteoporosis. Personalized Care of Trauma Patients. Personalized Medical Care of Astronauts during Space Flights. Personalized Management of Motion Sickness. Personalized Treatment of Rare
Diseases. Personalized Management of DNA Repair Disorders. Personalized Preventive Medicine and Public Health. Personalized Public Health. References. 378 379 379 379 380 380 380 381 381 382 382 383 383 383 384 384 385 387 387 387 387 388 388 388 388 388 390 391 391 392 392 392 393 393 394 395 395 396 396 399 399 400 400
Contents χχ։ϋ 19 Principles of Personalized Oncology. Introduction. Epidemiology of Cancer. Development of Personalized Therapy in Cancer. Molecular Biology of Cancer as Basis for Personalized Management. Challenges of Cancer Classification. Role of Staging in Personalized Management of Cancer. Systems Biology of Cancer. Relationships of Technologies for Personalized Management of Cancer. Role of Molecular Diagnostics in the Management of Cancer. A Universal NGS-Based Oncology Test System. Analysis of RNA Splicing Events in Cancer. Analysis of Chromosomal Alterations in Cancer Cells. Cancer Classification Using Microarrays. Cancer Gene Panel for Detection of Genetic Alterations. Companion Diagnostics for Cancer. Circulating Tumor Cells Isolation and Characterization. Circulating Cell-Free DNA for Monitoring Personalized Cancer Therapy. Detection of Loss of Heterozygosity. Detection of Rare Mutations to Guide
Cancer Therapy. Diagnostics for Detection of Minimal Residual Disease. DNA Repair Biomarkers. DNA Sequencing for Prognosis of Cutaneous T Cell Lymphoma. Fluorescent In Situ Hybridization. Gene Expression Profiling. Synthetic Lethality. GPS Cancer Test. Liquid Biopsy. Modulation of CYP450 Activity for Cancer Therapy. NanoFlares for Detection of CTCs. Pathway-Based Analysis of Cancer. Quantum Dot-Based Test for DNA Méthylation. Role of Molecular Imaging in Personalized Therapy of Cancer. Unraveling the Genetic Code of Cancer. Cancer Prognosis. Personalized Cancer Prevention. Detection of Mutations for Cancer Risk Assessment and Prevention. Impact of Biomarkers on Management of Cancer. Biomarker-Based
Assays for Predicting Response to Anticancer Therapeutics. HER-2/neu Oncogene as a Biomarker for Cancer. 403 403 403 403 403 408 409 409 410 410 411 412 412 412 413 413 413 414 415 415 416 416 416 417 417 419 419 420 420 421 421 422 422 425 425 426 426 427 427 427
Contents XXIV L-Asparaginase Treatment of Cancer Guided by a Biomarker. miRNA Biomarkers for Personalized Management of Cancer. Oncogene GOLPH3 as a Cancer Biomarker. Predictive Biomarkers for Efficacy of Anticancer Therapy . Sequencing to Discover Biomarkers to Personalize Cancer Treatment. Swiss Molecular Tumor Board for Individualized, Biomarker-Based Decisions. VeraTag™ Assay System for Cancer Biomarkers. Determination of Response to Therapy. Ex Vivo Testing of Tumor Biopsy for Chemotherapy Sensitivity. Genomic Approaches to Predict Response to Anticancer Agents. Non-genetic Factors for Variations in Response of Cancer Cells to Drugs. Profiling of Cancer Therapy in Zebrafish Xenografts to Predict Response. Proteomic Analysis of Tumor Biopsies to Predict Response to Treatment. Real-Time Apoptosis
Monitoring. Serum Nucleosomes as Indicators of Sensitivity to Chemotherapy. Targeted Microbubbles to Tumors for Monitoring Anticancer Therapy. PET Imaging for Determining Response to Chemotherapy. Concluding Remarks About Predicting Response to Anticancer Therapy. Molecular Diagnostics Combined with Cancer Therapeutics. Aptamers for Combined Diagnosis and Therapeutics of Cancer. Combining Diagnosis and Therapy of Metastatic Cancer . Detection and Destrucdon of CTCs with Nanoparticles and X-Rays. Molecular Profiling of Cancer. Targeted Cancer Therapies. Targeting Angiogenesis in Cancer. Targeting Glycoproteins on Cell Surface. Targeting Pathways in Cancer. Targeted Personalized Anticancer Medicines in Clinical Use. Personalized Radiation Therapy.
Peptide Receptor Radionuclide Therapy. Use of Radiation Sensitivity Biomarkers in Personalized Radiotherapy. Use of Imaging to Monitor Radioimmunotherapy of Non-Hodgkin Lymphoma. 428 428 429 429 429 430 430 430 431 431 434 434 434 435 435 435 436 437 437 437 438 439 439 439 439 440 440 440 440 442 442 443
xxv Contents Role of Nanobiotechnology in Personalized Management of Cancer. Selective Destruction of Cancer Cells While Sparing Normal Cells. Tissue Systems Biology Approach to Personalized Management of Cancer. Role of Oncoproteomics in Personalized Therapy of Cancer. . . Cancer Tissue Proteomics. Proteomics Technologies to Guide Targeted Drug Selection for Cancer. Role of Metabolomics in Personalized Therapy of Cancer. Manipulation of Tumor Metabolism for Personalizing Antitumor Effect. Role of Sequencing in Personalized Therapy of Cancer. Pharmacogenomic-Based Chemotherapy. Whole Genome Technology to Predict Drug Resistance. Anticancer Drug Selection Based on Molecular Characteristics of Tumor. Testing Microsatellite-Instability for Response to Chemotherapy. Pharmacogenetics of Cancer Chemotherapy. CYP1A2. Thiopurine
Methyltransferase. Dihydropyrimidine Dehydrogenase. UGT1A1 Test as Guide to Irinotecan Therapy. Computers and Digital Technologies for Personalized Oncology. Artificial Intelligence in Personalized Management of Cancer. Computational Models of Kinetically Tailored Treatment. Mathematical Modeling of Tumor Microenvironments. Modeling Signaling Pathways to Reposition Anticancer Drugs. Personalized Computational Oncology. Therapy Resistance in Cancer. Mechanism of Therapy Resistance in Cancer. Detection of Drug Resistance. Management of Drug Resistance in Cancer. Personalized Therapy of Cancer Metastases. Technologies for Analysis of CTCs. Systemic Antitumor Effect of Localized Radiotherapy for Cancer Metastases. Diagnosis of Cancer of an Unknown Primary. Current Trends and Future of Personalized Oncology.
Challenges for Developing Personalized Cancer Therapies. Personalizing Anticancer Drug Combinations. Cancer Genome Atlas. Cancer Moonshot. COLTHERES Consortium. 443 444 445 445 445 446 447 447 448 449 449 449 450 450 451 451 452 452 453 453 453 454 454 454 455 455 456 457 459 460 461 462 462 463 464 465 465 466
Contents XXVI Computer and Imaging Technologies for Personalizing Cancer Treatment. Genomic Cancer Care Alliance. Integrated Genome-Wide Analysis of Cancer for Personalized Therapy. International Cancer Genome Consortium. National Cancer Institute of US. Precision Oncology Decision Support at MD Anderson Cancer Center. PREDICT Consortium. Quebec Clinical Research Organization in Cancer. The San Antonio 1000 Cancer Genomes Project. Design of Future Personalized Cancer Therapies. Personalized Therapy of Cancer Based on Cancer Stem Cells. Role of CRISPR-Cas9 in Personalized Cancer Gene Therapy. Role of Epigenetics in Personalized Cancer Therapies. References. 20 Personalized Immuno-Oncology. Introduction.
Classification of Therapeutic Approaches in Immuno-Oncology. Role of Biomarkers in Personalized Immuno-Oncology. Organoids in Predicting Response to Immuno-Therapeutic Drugs. Role of Tumor-on-Chips in Immuno-Oncology. Role of Molecular Diagnostics and Sequencing in Immuno-Oncology. Genomic Testing. Gene Expression Signatures. Integration of Technologies for Personalized Immuno-Oncology. Factors that Drive the Development of Personalized Immunotherapy for Cancer. Computational Methods for Personalized Immuno-Oncology. Prediction of Response to Anti-PD-l/PD-Ll Therapy in Cancer. Monoclonal Antibodies for Personalized Management of Cancer. Targeted MAb-Based Immune therapy of Cancer. MAbs for Immune Activation. Immunotherapy of Dormant
Cancer. Antibody-Drug Conjugates for Personalized Therapy of Cancer. Combining Diagnostics with Therapeutics Based on MAbs. Immune Checkpoint Inhibitors for Cancer. 467 467 467 468 469 471 471 471 472 472 472 473 473 475 479 479 479 479 481 481 481 481 482 482 483 483 484 484 485 486 486 487 487 488
Contents xxvii Checkpoint Inhibitors Blocking PD-1 or PD-Ll. 488 Antibody Blocking the Cytotoxic T-Lymphocyte-Associated Protein 4. 489 Checkpoint Inhibitors Other than Anti-PD-Ll. 489 Personalizing Immune Checkpoint Inhibitor Therapy. 490 Cell-Based Immune Therapies. 490 Treatments for Cancer by Ex Vivo mobilization of Immune Cells. 490 Granulocytes as Anticancer Agents. 491 Neutrophil Granulocytes in MAb-Based Immunotherapy of Cancer. 491 Adoptive Cell Transfer. 491 Chimeric Antigen Receptor T Cells. 492 Cytokines. 492 Personalized Cancer Vaccines. 493 Antigen-Specific Vaccines. 493 Tumor-Derived Vaccines. 494 Patient-Specific Cell-Based Vaccines. 496 Adoptive Cell Therapy. 498 Personalized Peptide Cancer Vaccines. 500 Targeting Core
mutations in Cancer. 501 Current Status and Future of Personalized Cancer Vaccines . 501 Cytokines as Vaccine Adjuvants. 501 Limitations of Cancer Vaccination. 502 Role of neoantigens in Personalizing Cancer Vaccines. 503 Immunogene Therapy. 503 Delivery of Cancer Immunotherapy. 503 Nanoparticles for Delivery of Immunotherapy plus Photodynamic Therapy. 504 Synthetic Bacteria for Local Tumor Delivery of Checkpoint Blockade Nanobodies. 504 Transdermal Cold Atmospheric Plasma Mediated ICI Therapy. 504 Combination of Immunotherapies for Cancer. 505 Concluding Remarks and Future of Personalized Immuno-Oncology. 506 References. 506 21 Personalized Management of Cancers of Various Organs/Systems. 509 Introduction. 509 Personalized Management of Bladder
Cancer. 509 Personalized Management of Brain Tumors. 511 Personalized Management of Breast Cancer. 524 Personalized Management of Ovarian Cancer. 546 Personalized Management of Head and Neck Cancer. 553 Personalized Management of Hematological Malignancies. 554 Personalized Management of Gastrointestinal Tumors. 566 Personalized Management of Colorectal Cancer. 568 Personalized Management of Liver Cancer. 575
Contents xxviii 22 Personalized Management of Lung Cancer. Personalized Management of Malignant Melanoma. Personalized Management of Endocrine Tumors. Personalized Management of Osteosarcoma. Personalized Management of Pancreatic Cancer. Personlized Management of Prostate Cancer. Personalized Management of Thyroid Cancer. References. 577 585 587 590 591 592 596 596 Development of Personalized Medicine. Introduction. Drug Discovery and Development. Repositioning of Drugs for Personalized Medicine. Discovery of Personalized Medicines. Personalized Drug Delivery. Production and Distribution of Personalized Medicines. Role of Molecular Imaging in Personalized Medicine. Role of Genetic Banking Systems and Databases. Role of Biobanks in Development of Personalized Medicine . UK Biobank. Biobanking and Development of Personalized Medicine in EU. CARTaGENE for
Biobanks in Canada. Personalized Medicine Based on PhysioGenomics™ Technology. Role of Bioinformatics in Development of Personalized Medicine. Biosimulation Techniques for Developing Personalized Medicine. Biosensing and Wearable Devices for Monitoring of Health. Clinical Decision Support Systems. Digitalized Medicine. Genomic Data Analysis. Integration of Omics Data by Deep Learning. Health Information Management. Electronic Health Records. Personalized Prognosis of Disease. Personalized Approach to Clinical Trials. Adaptive Clinical Trials. Bayesian Approach in Biomarker-Based Clinical Trials. Clinical Trials of Therapeutics and Companion Diagnostics . Clinical Trials on Selected Subpopulations of Patients. Clinical Trials Networks. Creative Clinical Trial
Design. Individualzing Risks and Benefits in Clinical Trials. References. 603 603 603 603 604 604 604 605 608 608 609 609 609 610 610 612 612 613 613 613 614 614 614 618 618 619 620 621 622 622 622 623 623
Contents XXIX 23 24 Players in the Development of Personalized Medicine. Introduction. Personalized Medicine Coalition. Role of Pharmaceutical Industry. Role of Biotechnology Companies. Role of Life Sciences Industries. Role of Biomedical Engineering in Wearable Devices for Personalized Healthcare. Role of the Clinical Laboratories. Role of the US Government in Personalized Medicine. Precision Medicine Initiative. Department of Health and Human Services and Personalized Medicine. Agency for Healthcare Research and Quality. Comparative Effectiveness Research. Role of the US Government Agencies in Personalized Medicine. Role of Academic Institutions and Organizations in the US . Role of Academic Collaborations with Companies. Role of Healthcare Organizations. Role of the Medical
Profession. Role of Patients. Advantages of Personalized Medicine for Players. References. 625 625 625 625 627 627 Global Scope of Personalized Medicine. Global Alliance for Genomics and Health. Precision Medicine Project of World Economic Forum. Personalized Medicine in Canada. Personalized Medicine at Ontario Institute for Cancer Research. Personalized Medicine Partnership for Cancer in Quebec . Quebec Center of Excellence in Personalized Medicine. Personalized Medicine in the EU. European Personalized Medicine Diagnostics Association . . European Ubiquitous Pharmacogenomics Project. UK National Health Service and Medical Genetics. UK’s 100,000 Genomes Project. UK’s Precision Medicine Catapult. Personalized Medicine in France. Personalized Medicine in Germany. Personalized Medicine in Israel.
Personalized Medicine in Japan. Biobanks in Japan. Companion Diagnostics in Japan. Cost-Effectiveness of Personalized Medicine in Japan. 661 661 661 662 628 628 629 630 632 633 634 635 639 652 652 653 654 658 659 662 664 664 664 665 665 665 666 666 666 667 667 668 668 668 669
Contents xxx 25 26 27 Genetic Testing in Japan. Initiative on Rare and Undiagnosed Diseases. Personalized Medicine in the Developing Countries. Personalized Medicine in the Middle East. Personalized Medicine in China. Personalized Medicine in India. Personalized Medicine in Africa. 669 669 670 670 671 671 671 Ethical Issues in Personalized Medicine. Introduction to Ethical Issues. Ethical Issues of Pharmacogenetics. Ethical Aspects of Genetic Information. Ethical Issues of Whole Genome Analysis. Privacy Issues in Personalized Medicine. Genetic Information Nondiscrimination Act in theUS. UNESCO and Ethical Aspects of Personalized Medicine . Genotype-Specific Clinical Trials. Ethical Issues in Use of Digital Technologies for Personalized Medicine. Social Issues in Personalized Medicine. Disparities in Healthcare Among Various Populations.
Race and Personalized Medicine. Genetic Testing and Concerns About Disparities in Healthcare. Pharmacogenomics/Pharmacogenetics in Racial/Ethnic Populations. Racial and Ethnic Differences in Disease Epidemiology and Response to Therapy. Race and Cancer. Race and Alzheimer Disease. Race and Coronary Heart Disease. Race and Inflammatory Bowel Disease. Tackling Racial Issues and Improving Access to Genomic Medicine. References. 673 673 673 674 674 674 675 675 676 Legal Regulatory Aspects of Personalized Medicine. Legal Aspects of Personalized Medicine. Gene Patents and Personalized Medicine. Regulatory Aspects. FDA and Personalized Medicine. FDA and Molecular Diagnostics in Relation to Personalized Medicine. Regulatory
Aspects of Pharmacogenetics. Regulation of Direct-to-Consumer Genetic Testing. FDA and Pharmacogenomics. FDA and Predictive Medicine. References. 683 683 683 684 684 Economics of Personalized Medicine. Introduction. Personalized Medicine and Drug Markets. 701 701 701 676 677 677 677 678 678 679 680 680 680 680 681 681 685 691 692 695 699 700
Contents XXXI Perceived Financial Concerns. Personalized Medicine and Orphan Drug Syndrome. Commercial Aspects of Pharmacogenomics. Cost of DNA Testing. Cost of Sequencing the Human Genome. Cost of Genotyping. Cost of Pharmacogenomics-Based Clinical Trials. Business Development of Pharmacogenomic Companies . Cost of Personalized Healthcare. The Rising Healthcare Costs in the US. Genetic Testing and Cost of Healthcare. Personalized Medicine for Reducing Cost of Care of Cancer. Reducing Healthcare Costs by Combining Diagnostics with Therapeutics. Reducing the Cost of Treatment of Acte Myeloid Leukemia. Cost-Effectiveness of Personalized Medicine. Early Cost-Effectiveness Analysis of New Personalized Medicine Technologies. Cost-Effectiveness of Pharmacogenetic Testing. Cost-Effectiveness of CYP Genotyping-Based Pharmacotherapy. Cost Effectiveness of HIV Genotyping in
Treatment of AIDS. Cost-Effectiveness of Warfarin Pharmacogenomics. Overall Economic Impact of Personalized Medicine on Healthcare. References. 28 Future of Personalized Medicine. Introduction. Personal Genome Project. Translational Science and Personalized Medicine. Personalized Predictive Medicine. Connected Health and Personalized Medicine. Challenges and Opportunities for Personalized Medicine . Medicine in the Year 2025 . Concluding Remarks About the Future of Personalized Medicine. References. Index 701 702 702 702 702 704 705 705 705 705 706 706 708 708 709 709 709 710 710 711 711 711 713 713 713 715 717 717 718 722 723 724 725
Kewal К. Jain Textbook of Personalized Medicine Third Edition This book is for personalized medicine as a prescription of specific treatments and therapeutics best suited for an individual and considersgenetic as well as environmental factors that influence responses to therapy. Best approaches are described for integration of all available technologies for optimizing the therapy of individual patients. This comprehensive third edition covers the latest advances in personalized medicine and several chapters are devoted to various specialties, particular}՛ cancer which is the largest area of application. The book discusses the development of personalized medicine and various playersin it such as companies, academic institutions, the government, and the public as the consumer of healthcare. Additionally, the roles of bioinformatics, electronic health records, and digital technologies for personalized medicine are discussed. Textbook of Personalized Medicine, 3rd Edition serves as a convenient source of information for students at many levels and in a wide range of fields, including physicians, scientists, and decision makers in the biopharmaceutical and healthcare industries. |
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| spelling | Jain, Kewal K. 1937- Verfasser (DE-588)114376093 aut Textbook of personalized medicine Kewal K. Jain Third edition Cham, Switzerland Springer [2021] © 2021 xliii, 744 Seiten Diagramme txt rdacontent n rdamedia nc rdacarrier Internal medicine Pharmacotherapy Pharmacology Medicine Pharmakogenetik (DE-588)4271255-5 gnd rswk-swf Individualisierte Medizin (DE-588)7660544-9 gnd rswk-swf Pharmakogenetik (DE-588)4271255-5 s Individualisierte Medizin (DE-588)7660544-9 s DE-604 Erscheint auch als Online-Ausgabe 978-3-030-62080-6 Digitalisierung UB Augsburg - ADAM Catalogue Enrichment application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=032491315&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis Digitalisierung UB Augsburg - ADAM Catalogue Enrichment application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=032491315&sequence=000003&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA Klappentext |
| spellingShingle | Jain, Kewal K. 1937- Textbook of personalized medicine Internal medicine Pharmacotherapy Pharmacology Medicine Pharmakogenetik (DE-588)4271255-5 gnd Individualisierte Medizin (DE-588)7660544-9 gnd |
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| title | Textbook of personalized medicine |
| title_auth | Textbook of personalized medicine |
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| title_full | Textbook of personalized medicine Kewal K. Jain |
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| title_full_unstemmed | Textbook of personalized medicine Kewal K. Jain |
| title_short | Textbook of personalized medicine |
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| topic | Internal medicine Pharmacotherapy Pharmacology Medicine Pharmakogenetik (DE-588)4271255-5 gnd Individualisierte Medizin (DE-588)7660544-9 gnd |
| topic_facet | Internal medicine Pharmacotherapy Pharmacology Medicine Pharmakogenetik Individualisierte Medizin |
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