• Japanese
  • Korean
  • Chinese
Cover Image

Personalized Medicine - scientific & commercial aspects

Notes

This report describes the latest concepts of development of personalized medicine based on pharmacogenomics, pharmacogenetics, pharmacoproteomics, and metabolomics. The bibliography contains over 630 selected publications cited in the report.

The aim of personalized medicine or individualized treatment is to match the right drug to the right patient and, in some cases, even to design the appropriate treatment for a patient according to his/her genotype. This report describes the latest concepts of development of personalized medicine based on pharmacogenomics, pharmacogenetics,pharmacoproteomics, and metabolomics. Basic technologies of molecular diagnostics play an important role, particularly those for single nucleotide polymorphism (SNP) genotyping. Diagnosis is integrated with therapy for selection of the treatment as well for monitoring the results. Biochip/microarray technologies are also important and finally bioinformatics is needed to analyze the immense amount of data generated by various technologies.

Pharmacogenetics, the study of influence of genetic factors on drug action and metabolism, is used for predicting adverse reactions of drugs. Several enzymes are involved in drug metabolism of which the most important ones are those belonging to the family of cytochrome P450. The knowledge of the effects of polymorphisms of genes for the enzymes is applied in drug discovery and development as well as in clinical use of drugs. Cost-effective methods for genotyping are being developed and it would be desirable to include this information in the patient's record for the guidance of the physician to individualize the treatment. Pharmacogenomics, a term that overlaps with pharmacogenetics but is distinct, deals with the application of genomics to drug discovery and development. It involves the mechanism of action of drugs on cells as revealed by gene expression patterns. Pharmacoproteomics is an important contribution to personalized medicine as it is a more functional representation of patient-to-patient variation than that provided by genotyping.A 'pharmacometabonomic' approach to personalizing drug treatment is also described.

Biological therapies such as those which use patient's own cells are considered to be personalized medicines. Vaccines are prepared from individual patient's tumor cells. Individualized therapeutic strategies using monoclonal bodies can be directed at specific genetic and immunologic targets. Ex vivo gene therapy involves the genetic modification of the patient's cells in vitro, prior to reimplantation of these cells in the patient's body.

Various technologies are integrated to develop personalized therapies for specific therapeutic areas described in the report. Examples of this are genotyping for drug resistance in HIV infection, personalized therapy of cancer, antipsychotics for schizophrenia, antidepressant therapy, antihypertensive therapy and personalized approach to neurological disorders. Although genotyping is not yet a part of clinically accepted routine, it is expected to have this status by the year 2018.

Several players are involved in the development of personalized therapy. Pharmaceutical and biotechnology companies have taken a leading role in this venture in keeping with their future role as healthcare enterprises rather than mere developers of technologies and manufacturers of medicines.

Ethical issues are involved in the development of personalized medicine mainly in the area of genetic testing. These along with social issues and consideration of race in the development of personalized medicine are discussed. Regulatory issues are discussed mainly with reference to the FDA guidelines on pharmacogenomics.

Increase in efficacy and safety of treatment by individualizing it has benefits in financial terms. Information is presented to show that personalized medicine will be cost-effective in healthcare systems. For the pharmaceutical companies, segmentation of the market may not leave room for conventional blockbusters but smaller and exclusive markets for personalized medicines would be profitable. Marketing opportunities for such a system are described with market estimates from 2013-2023.

Profiles of 312 companies involved in developing technologies for personalized medicines, along with 562 collaborations are included in the part II of the report. Finally the bibliography contains over 750 selected publications cited in the report.The report is supplemented by 71 tables and 25 figures.

Table of Contents

Part I

0. Executive Summary 21

1. Basic Aspects 23

  • Definition of personalized medicine 23
  • History of medical concepts relevant to personalized medicine 24
  • Molecular biological basis of personalized medicine 26
  • The human genome 26
  • ENCODE 27
  • Chromosomes 27
  • Genes 28
  • The genetic code 28
  • Gene expression 28
  • DNA sequences and structure 29
  • Genetic variations in the human genome 29
  • Single nucleotide polymorphisms 30
  • Copy number variations in the human genome 30
  • Insertions and deletions in the human genome 32
  • Large scale variation in human genome 33
  • Structural variations in the human genome 33
  • Mapping and sequencing of structural variation from human genomes 34
  • 1000 Genomes Project 35
  • Role of DNA sequencing in the development of personalized medicine 36
  • Human Variome Project 36
  • Interconnected genetic and genomic patterns in human diseases 37
  • Basics technologies for developing personalized medicine 38
  • Definitions of technologies relevant to personalized medicine 38
  • Problems with the ICH definitions of pharmacogenomics and pharmacogenetics 38
  • 'Omics' and personalized medicine 39
  • Relationship of various technologies to personalized medicine 39
  • Conventional medicine versus personalized medicine 40
  • Personalized medicine and evidence-based medicine 40
  • Role of genetics in future approaches to healthcare 40
  • Genetic medicine 40
  • Human disease and genes 41
  • Genetic and environmental interactions in etiology of human diseases 41
  • Role of genetics in development of personalized medicines 42
  • Genetic databases 42
  • Clinical Genomic Database 42
  • Genetic epidemiology 43
  • Limitations of medical genetics and future prospects 43
  • Genetics vs. epigenetics 44
  • Role of systems biology in personalized medicine 44
  • Systems pharmacology 45
  • Systems medicine 46
  • Synthetic biology and development of personalized medicines 46
  • A personalized approach to environmental factors in disease 47
  • Reclassification of diseases 48
  • Translational science and personalized medicine 49

2. Molecular Diagnostics in Personalized Medicine 51

  • Introduction 51
  • Molecular diagnostic technologies 51
  • PCR-based methods 52
  • DirectLinear™ Analysis 52
  • Denaturing high-performance liquid chromatography 53
  • Multiplex Allele-Specific Diagnostic Assay 53
  • Representational oligonucleotide microarray analysis 53
  • Restriction fragment length polymorphism (RFLP) 53
  • Real-time PCR for detection of CNVs 54
  • Non-PCR methods 54
  • Arrayed primer extension (APEX) 54
  • Enzymatic Mutation Detection (EMD) 54
  • DNA sequencing 54
  • Sanger-sequencing technology 55
  • ABI PRISM® 310 Genetic Analyzer 56
  • High-throughput paired end transcriptome sequencing 56
  • Emerging sequencing technologies 56
  • 4300 DNA analyzer 57
  • Apollo 100 57
  • "Color blind" approach to DNA sequencing 58
  • Cyclic array sequencing 58
  • CEQ™ 8000 58
  • DeepCAGE sequencing 58
  • Electron microscope-based DNA sequencing 59
  • Genometrica™ sequencer 59
  • GS-FLEX system (Roche/454) 60
  • IBS sequencing technology 61
  • Illumina's sequencing technology 61
  • MegaBACE 500 62
  • Microdroplet-based PCR for large-scale targeted sequencing 62
  • Multiplex amplification of human DNA sequences 63
  • Nanoscale sequencing 63
  • Polonator sequencer 63
  • RainStorm™ microdroplet technology 64
  • Sequential DEXAS 64
  • SOLiD technology 65
  • Sequencing by hybridization 66
  • Whole genome sequencing 66
  • Bioinformatic tools for analysis of genomic sequencing data 67
  • Detection of single molecules in real time 67
  • Direct observation of nucleotide incorporation 67
  • Molecular Combing 67
  • Nanopore sequencing 67
  • DNA sequence by use of nanoparticles 68
  • Zero-mode waveguide nanostructure arrays 68
  • Future prospects of sequencing 68
  • Role of sequencing in development of personalized medicine 69
  • Biochips and microarrays 70
  • Role of biochip/microarray technology in personalized medicine 71
  • Applications of biochip/microarray technology in personalized medicine 71
  • Standardizing the microarrays 72
  • Biochip technologies 73
  • GeneChip 73
  • AmpliChip CYP450 73
  • Microfluidics 75
  • Lab-on-a-chip 75
  • Micronics' microfluidic technology 75
  • LabCD 76
  • Microfluidic automated DNA analysis using PCR 76
  • Integrated microfluidic bioassay chip 76
  • Electronic detection of nucleic acids on microarrays 77
  • Strand displacement amplification on a biochip 77
  • Rolling circle amplification on DNA microarrays 77
  • Universal DNA microarray combining PCR and ligase detection reaction 78
  • Protein biochips 78
  • ProteinChip 78
  • LabChip for protein analysis 79
  • TRINECTIN proteome chip 79
  • Protein expression microarrays 80
  • Microfluidic devices for proteomics-based diagnostics 80
  • New developments in protein biochips/microarrays 81
  • Protein biochips/microarrays for personalized medicine 81
  • SNP genotyping 82
  • Genotyping and haplotyping 83
  • Haplotype Specific Extraction 83
  • Computation of haplotypes 84
  • HapMap project 84
  • Haplotyping for whole genome sequencing 85
  • Predictingdrug response with HapMap 85
  • Companies developing haplotyping technology 86
  • Technologies for SNP analysis 86
  • Biochip and microarray-based detection of SNPs 87
  • SNP genotyping by MassARRAY 87
  • Biochip combining BeadArray and ZipCode technologies 88
  • SNP-IT primer-extension technology 88
  • Affymetrix Variation Detection Arrays 88
  • Use of NanoChip for detection of SNPs 88
  • Electrochemical DNA probes 89
  • Single base extension-tag array 89
  • Laboratory Multiple Analyte Profile 89
  • PCR-CTPP (confronting two-pair primers) 90
  • SNP genotyping on a genome-wide amplified DOP-PCR template 90
  • TaqMan real-time PCR 90
  • Non-Enzymatic Amplification Technology 91
  • SNP genotyping with gold nanoparticle probes 91
  • Locked nucleic acid 91
  • Molecular inversion probe based assays 92
  • Pyrosequencing 92
  • Reversed enzyme activity DNA interrogation test 92
  • Smart amplification process version 2 93
  • Zinc finger proteins 93
  • UCAN method (Takara Biomedical) 94
  • Mitochondrial SNPs 94
  • Limitations of SNP in genetic testing 94
  • Concluding remarks on SNP genotyping 94
  • Companies involved in developing technologies/products for SNP analysis 95
  • Impact of SNPs on personalized medicine 96
  • Detection of copy number variations 97
  • Study of rare variants in pinpointing disease-causing genes 97
  • Optical Mapping 98
  • Role of nanobiotechnology in molecular diagnostics 98
  • Cantilevers for personalized medical diagnostics 99
  • Nanopore-based technology for single molecule identification 99
  • Role of biomarkers in personalized medicine 100
  • Biomarkers for diagnostics 100
  • Biomarkers for drug development 101
  • Application of proteomics in molecular diagnosis 101
  • Proteomic strategies for biomarker identification 101
  • Proteomic technologies for detection of biomarkers in body fluids 101
  • Protein patterns 102
  • Layered Gene Scanning 102
  • Comparison of proteomic and genomic approaches in personalized medicine 103
  • Gene expression profiling 103
  • DNA microarrays 104
  • Analysis of single-cell gene expression 104
  • Gene expression profiling based on alternative RNA splicing 105
  • Whole genome expression array 106
  • Tangerine™ expression profiling 106
  • Gene expression analysis on biopsy samples 107
  • Profiling gene expression patterns of white blood cells 107
  • Serial analysis of gene expression (SAGE) 108
  • Multiplexed Molecular Profiling 108
  • Gene expression analysis using competitive PCR and MALDI TOF MS 109
  • Monitoring in vivo gene expression by magnetic resonance imaging 109
  • Companies involved in gene expression analysis 109
  • Monitoring in vivo gene expression by molecular imaging 110
  • Molecular imaging and personalized medicine 111
  • Glycomics-based diagnostics 111
  • Combination of diagnostics and therapeutics 111
  • Use of molecular diagnostics for stratification in clinical trials 112
  • Companion diagnostics 112
  • Companies involved in companion diagnostics 113
  • Point-of-care diagnosis 115
  • Companies developing point-of-care diagnostic technologies 116
  • Point-of-care diagnosis of infections 118
  • Advantages versus disadvantages of point-of-care diagnosis 118
  • Future prospects of point-of-care diagnosis 119
  • Genetic testing for disease predisposition 119
  • Preventive genetics by early diagnosis of mitochondrial diseases 120
  • Direct-to-consumer genetic services 120
  • Role of diagnostics in integrated healthcare 121
  • Concept of integrated healthcare 121
  • Components of integrated healthcare 122
  • Screening 122
  • Disease prediction 122
  • Early diagnosis 122
  • Prevention 122
  • Therapy based on molecular diagnosis 122
  • Monitoring of therapy 123
  • Advantages and limitations of integrated healthcare 123
  • Commercially available systems for integrated healthcare 123
  • Future of molecular diagnostics in personalized medicine 124

3. Pharmacogenetics 125

  • Basics of pharmacogenetics 125
  • Role of molecular diagnostics in pharmacogenetics 126
  • Role of pharmacogenetics in pharmaceutical industry 127
  • Study of the drug metabolism and pharmacological effects 127
  • Causes of variations in drug metabolism 127
  • Enzymes relevant to drug metabolism 128
  • Pharmacogenetics of phase I metabolism 128
  • CYP450 128
  • P450 CYP 2D6 inhibition by selective serotonin reuptake inhibitors 130
  • Cytochrome P450 polymorphisms and response to clopidogrel 131
  • Lansoprazole and cytochrome P450 131
  • Glucose-6-phosphate dehydrogenase 131
  • Pharmacogenetics of phase II metabolism 132
  • N-Acetyltransferase 132
  • Uridine diphosphate-glucuronosyltransferase 133
  • Measurement of CYP isoforms 133
  • Polymorphism of drug transporters 134
  • Genetic variation in drug targets 134
  • Polymorphisms of kinase genes 135
  • Effect of genetic polymorphisms on disease response to drugs 135
  • Ethnic differences in drug metabolism 136
  • Gender differences in pharmacogenetics 136
  • Role of pharmacogenetics in drug safety 137
  • Adverse drug reactions 137
  • Adverse drug reactions in children 138
  • Adverse drug reactions related to toxicity of chemotherapy 138
  • Genetically determined adverse drug reactions 138
  • Malignant hyperthermia 140
  • Pharmacogenetics of clozapine-induced agranulocytosis 140
  • Role of pharmacogenetics in warfarin therapy 140
  • Role of pharmacogenetics in antiplatelet therapy 141
  • Role of pharmacogenetics in carbamazepine therapy 143
  • Role of pharmacogenetics in statin therapy 143
  • FDA consortium linking genetic biomarkers to serious adverse events 144
  • Therapeutic drug monitoring, phenotyping, and genotyping 144
  • Therapeutic drug monitoring 145
  • Phenotyping 145
  • Genotyping 146
  • Genotyping vs phenotyping 146
  • Phenomics 147
  • Limitations of genotype-phenotype association studies 148
  • Molecular toxicology in relation to personalized medicines 148
  • Toxicogenomics 148
  • Biomarkers of drug toxicity 148
  • Drug-induced mitochondrial toxicity 149
  • Companies involved in molecular toxicology 149
  • Gene expression studies 150
  • Pharmacogenetics in clinical trials 150
  • Postmarketing pharmacogenetics 151
  • Clinical implications of pharmacogenetics 151
  • Application of CYP450 genotyping in clinical practice 151
  • Pharmacogenomic biomarker information in drug labels 151
  • Genotype-based drug dose adjustment 155
  • Use of pharmacogenetics in clinical pharmacology 155
  • Application of CYP2C19 pharmacogenetics for personalized medicine 155
  • Genotyping for identifying responders to sulfasalazine 156
  • HLA alleles associated with lumiracoxib-related liver injury 156
  • Pharmacogenetic basis of thiopurine toxicity 156
  • Tranilast-induced hyperbilirubinemia due to gene polymorphism 157
  • Linking pharmacogenetics with pharmacovigilance 157
  • Genetic susceptibility to ADRs 157
  • Linking genetic testing to postmarketing ADR surveillance 157
  • Recommendations for the clinical use of pharmacogenetics 158
  • Limitations of pharmacogenetics 158
  • Pharmacoepigenomics vs pharmacogenetics in drug safety 159
  • Future role of pharmacogenetics in personalized medicine 159

4. Pharmacogenomics 161

  • Introduction 161
  • Basics of pharmacogenomics 162
  • Pharmacogenomics and drug discovery 162
  • Preclinical prediction of drug efficacy 164
  • Pharmacogenomics and clinical trials 164
  • Impact of genetic profiling on clinical studies 165
  • Limitations of the pharmacogenomic-based clinical trials 166
  • Pharmacogenomic aspects of major therapeutic areas 167
  • Oncogenomics 167
  • Oncogenes 167
  • Tumor suppressor genes 168
  • Cardiogenomics 169
  • Neuropharmacogenomics 171
  • Pharmacogenomics of Alzheimer's disease 171
  • Pharmacogenomics of depression 172
  • Pharmacogenomics of schizophrenia 172
  • Companies involved in neurogenomics-based drug discovery 173
  • Current status and future prospects of pharmacogenomics 173

5. Role of Pharmacoproteomics 175

  • Basics of proteomics 175
  • Proteomic approaches to the study of pathophysiology of diseases 175
  • Single cell proteomics for personalized medicine 176
  • Diseases due to misfolding of proteins 176
  • Therapies for protein misfolding 177
  • Significance of mitochondrial proteome in human disease 177
  • Proteomic technologies for drug discovery and development 178
  • Role of reverse-phase protein microarray in drug discovery 178
  • Role of proteomics in clinical drug safety 178
  • Toxicoproteomics 178
  • Applications of pharmacoproteomics in personalized medicine 180

6. Role of Metabolomics in Personalized Medicine 181

  • Metabolomics and metabonomics 181
  • Metabolomics bridges the gap between genotype and phenotype 181
  • Metabolomics, biomarkers and personalized medicine 182
  • Metabolomic technologies 182
  • Urinary profiling by capillary electrophoresis 183
  • Lipid profiling 183
  • Role of metabolomics in biomarker identification and pattern recognition 184
  • Validation of biomarkers in large-scale human metabolomics studies 184
  • Pharmacometabonomics 184
  • Metabonomic technologies for toxicology studies 185
  • Metabonomics/metabolomics and personalized nutrition 185

7. Personalized Biological Therapies 187

  • Introduction 187
  • Recombinant human proteins 187
  • Therapeutic monoclonal antibodies 187
  • Cell therapy 188
  • Autologous tissue and cell transplants 188
  • Stem cells 188
  • iPSCs for personalized cell therapy 188
  • Role of stem cells derived from unfertilized embryos 188
  • Cloning and personalized cell therapy 189
  • Use of stem cells for drug testing 189
  • Gene therapy 189
  • Stem cell-based personalized gene therapy for cancer 190
  • Personalized vaccines 190
  • Personalized vaccines for viral diseases 190
  • Personalized cancer vaccines 190
  • Antisense therapy 191
  • RNA interference 191
  • MicroRNAs 192

8. Personalized Non-pharmacological Therapies 193

  • Introduction 193
  • Acupuncture 193
  • Personalized acupuncture therapy 193
  • Personalized hyperbaric oxygen therapy 194
  • Personalized nutrition 194
  • Nutrigenomics 195
  • Genomics of vitamin D and calcium supplementation 195
  • Nutrigenomics and functional foods 196
  • Nutrigenetics and personalized medicine 196
  • Nutrigenomics and personalized medicine 197
  • Nutrition and proteomics 197
  • Personalized diet prescription 197
  • Personalized physical exercise 198
  • Variations in response to aerobic exercise 198
  • Variations in exercise-induced muscle hypertrophy and strength 199
  • Personalized surgery 199

9. Personalized Medicine in Major Therapeutic Areas 201

  • Introduction 201
  • Personalized management of infections 202
  • Management of HIV 202
  • CD4 counts as a guide to drug therapy for AIDS 202
  • Drug-resistance in HIV 202
  • Genetics of human susceptibility to HIV infection 203
  • Measurement of Replication Capacity 204
  • Personalized vaccine for HIV 204
  • Prevention of adverse reactions to antiviral drugs 204
  • Pharmacogenetics and HIV drug safety 205
  • Pharmacogenomics of antiretroviral agents 205
  • Role of diagnostic testing in management of HIV 206
  • Role of genetic variations in susceptibility to HIV-1 206
  • Role of personalized HIV therapy in controlling drug resistance 207
  • Sequencing for personalizing HIV therapy 207
  • Personalized treatment of hepatitis B 208
  • Personalized treatment of hepatitis C 208
  • Responders vs non-responders to treatment for hepatitis C 209
  • Drug resistance in hepatitis C 210
  • Personalized management of tuberculosis 210
  • Personalized management of fungal infections 210
  • Psychiatric disorders 211
  • Psychopharmacogenetics/psychopharmacodynamics 212
  • Serotonin genes 212
  • Calcium channel gene 212
  • Dopamine receptor genes 212
  • COMT genotype and response to amphetamine 212
  • Methylenetetrahydrofolate reductase 213
  • Genotype and response to methylphenidate in children with ADHD 213
  • GeneSight tests for individualized therapy of psychiatric disorders 213
  • Personalized antipsychotic therapy 214
  • Personalized antidepressant therapy 216
  • EEG to predict adverse effects and evaluate antidepressant efficacy 217
  • Individualization of SSRI treatment 217
  • Role of protein sFRP3 in predicting response to antidepressants 219
  • Treatment resistant depression 219
  • Vilazodone with a test for personalized treatment of depression 219
  • Neurological disorders 220
  • Personalized management of Alzheimer's disease 220
  • Personalized management of Parkinson's disease 221
  • Discovery of subgroup-selective drug targets in PD 222
  • Personalized cell therapy for PD 222
  • Personalized management of epilepsy 223
  • Biomarkers of epilepsy 223
  • Genetics/genomics of epilepsy 224
  • Choice of the right AED 225
  • Adverse effects of AEDs 226
  • Pharmacogenomics of epilepsy 226
  • Drug resistance in epilepsy 227
  • An algorithm for personalized management of epilepsy 229
  • Future prospects for management of epilepsy 229
  • Personalized management of migraine 230
  • Individualization of use of triptans for migraine 230
  • Multitarget therapeutics for personalized treatment of headache 231
  • Personalized management of stroke 231
  • Application of proteomics for personalizing stroke management 231
  • Brain imaging in trials of restorative therapies for stroke 232
  • Decisions for evacuation of intracerebral hemorrhage 232
  • Revascularization procedures in chronic post-stroke stage 232
  • Personalized treatment of multiple sclerosis 233
  • Immunopathological patterns of demyelination for assessing therapy 233
  • Personalizing mitoxantrone therapy of multiple sclerosis 234
  • Fusokine method of personalized cell therapy of multiple sclerosis 234
  • MBP8298 234
  • Pharmacogenomics of IFN-β therapy in multiple sclerosis 235
  • T cell-based personalized vaccine for MS 236
  • Personalized management of pain 236
  • Genetic factors in response to pain 237
  • Genetic mutations with loss of pain 238
  • Pharmacogenetics/pharmacogenomics of pain 238
  • Personalized management of pain with opioids 239
  • Pharmacogenetics of NSAIDs 240
  • Mechanism-specific management of pain 240
  • Preoperative testing to tailor postoperative analgesic requirements 240
  • Personalized analgesics 241
  • Signature of pain on brain imaging 241
  • Concluding remarks on personalized management of pain 241
  • Personalized management of sleep disorders 242
  • Personalized therapy of insomnia 243
  • Cardiovascular disorders 243
  • Role of diagnostics in personalized management of cardiovascular disease 243
  • Cardiovascular disorders with a genetic component 243
  • Gene mutations associated with risk of coronary heart disease 245
  • Gene variant as a risk factor for sudden cardiac death 245
  • KIF6 gene test as a guide to management of heart disease 246
  • NGS sequencing for management of cardiovascular disorders 246
  • Testing in coronary heart disease 247
  • Biomarkers and personalized management of cardiovascular disorders 248
  • Pharmacogenomics of cardiovascular disorders 248
  • Modifying the genetic risk for myocardial infarction 248
  • Personalized management of chronic myocardial ischemia 249
  • Management of chronic angina pectoris 249
  • Management of heart failure 250
  • β-blockers 250
  • Bucindolol 250
  • BiDil 251
  • Management of hypertension 251
  • Adjusting therapy of hypertension to fluctuations of blood pressure 252
  • Choice of drugs for hypertension 252
  • Correction of causes and risk factors of hypertension 252
  • Genes and hypertension 253
  • Improving management of HPN by targeting new pathways 253
  • Individualized therapy of HPN based on risk factors of heart disease 253
  • Pharmacogenomics of diuretic drugs 254
  • Pharmacogenomics of ACE inhibitors 254
  • Prediction of antihypertensive activity of rostafuroxin 254
  • Role of pharmacogenetics in management of hypertension 255
  • Scheme for management of hypertension by personalized approach 256
  • Pharmacogenetics of lipid-lowering therapies 256
  • Polymorphisms in genes involved in cholesterol metabolism 256
  • Role of eNOS gene polymorphisms 257
  • Prediction of response to statins 257
  • Personalized management of women with hyperlipidemia 258
  • Thrombotic disorders 258
  • Factor V Leiden mutation 258
  • Anticoagulant therapy 259
  • Antiplatelet therapy 260
  • Nanotechnology-based personalized therapy of cardiovascular diseases 261
  • Project euHeart for personalized management of heart disease 261
  • Concluding remarks on personalized management of cardiovascular diseases 262
  • Personalized management of pulmonary disorders 262
  • Role of genetic ancestory in lung function 262
  • Personalized therapy of asthma 262
  • Biomarkers for predicting response to corticosteroid therapy 263
  • Genetic polymorphism and response to β2-adrenergic agonists 263
  • Genotyping in asthma 263
  • IgE as guide to dosing of omalizumab for asthma 264
  • Lebrikizumab for personalised treatment of asthma 265
  • Personalized management of chronic obstructive pulmonary disease 265
  • Personalized management of skin disorders 266
  • Genetic testing for personalized skin care 266
  • Management of hair loss based on genetic testing 266
  • Personalized therapy of rheumatoid arthritis 267
  • Genetics and epigenetic aspects of rheumatoid arthritis 267
  • Variations in the effectiveness of therapies for RA 267
  • Biomarkers for personalizing therapy of rheumatoid arthritis 268
  • DIATSTAT™ anti-cyclic citrullinated peptides in rheumatoid arthritis 268
  • Personalization of COX-2 inhibitor therapy 269
  • Personalization of infliximab therapy 269
  • Personalized therapy of RA guided by anti-citrullinated protein antibodies 269
  • Personalized approaches in immunology 270
  • Role of Mannose-binding lectin in personalized medicine 270
  • Pharmacogenetics and pharmacogenomics of immunosuppressive agents 270
  • Personalized management of patients with lupus erythematosus 271
  • Personalized management of diabetes 271
  • Management of genetic disorders 272
  • Personalized treatment of cystic fibrosis 273
  • Personalized management of gastrointestinal disorders 274
  • Personalized therapy of inflammatory bowel disease 274
  • Personalized management of lactose intolerance 274
  • Personalized approaches to improve organ transplantation 275
  • Personalization of kidney transplantation 275
  • Personalization of cardiac transplantation 275
  • Prediction of rejection for personalizig anti-rejection treatment 276
  • Personalized immunosuppressant therapy in organ transplants 276
  • Role of immunological biomarkers in monitoring grafted patients 277
  • Improved matching of blood transfusion 278
  • Personalized approach to addiction 279
  • Pharmacogenetics of drug addiction 279
  • Genetic polymorphism and management of alcoholism 279
  • Personalized therapy for smoking cessation 280
  • Antidepressant therapy for smoking cessation 281
  • Effectiveness of nicotine patches in relation to genotype 281
  • Personalized approaches to miscellaneous problems 281
  • Hormone replacement therapy in women 281
  • Personalized treatment of malaria 282
  • Personalized management of osteoporosis 282
  • Personalized management of renal disease 283
  • Gene associated with end-stage renal disease 283
  • Personalized care of trauma patients 284
  • Personalized anticoagulation 284
  • Personalized preventive medicine 284

10. Personalized Therapy of Cancer 287

  • Introduction 287
  • Challenges of cancer classification 287
  • Relationships of technologies for personalized management of cancer 288
  • Impact of molecular diagnostics on the management of cancer 288
  • A universal NGS-based oncology test system 289
  • Analysis of RNA splicing events in cancer 289
  • Analysis of chromosomal alterations in cancer cells 290
  • Cancer classification using microarrays 290
  • Catalog of cancer genes for personalized therapy 291
  • Circulating cancer cell analysis for personalizing therapy 291
  • Detection of loss of heterozygosity 292
  • BEAMing technology for analysis of circulating tumor DNA 292
  • Diagnosis of cancer of an unknown primary 292
  • Diagnostics for detection of minimal residual disease 293
  • DNA repair biomarkers 293
  • Fluorescent in situ hybridization 293
  • Gene expression profiling 293
  • OnkoMatch tumor genotyping 295
  • Gene expression profiles predict chromosomal instability in tumors 295
  • Isolation and characterization of circulating tumor cells 295
  • Modulation of CYP450 activity for cancer therapy 296
  • NanoFlares for detection of CTCs 296
  • Pathway-based analysis of cancer 296
  • Conversion of gene-level information into pathway-level information 296
  • Personalized therapies based on oncogenic pathways signatures 296
  • Quantum dot-based test for DNA methylation 297
  • Role of molecular imaging in personalized therapy of cancer 297
  • Functional diffusion MRI 298
  • FDG-PET/CT for personalizing cancer treatment 298
  • Image-guided personalized drug delivery in cancer 299
  • Tumor imaging and elimination by targeted gallium corrole 299
  • Future prospects of molecular imaging in management of cancer 299
  • Unraveling the genetic code of cancer 300
  • Cancer prognosis 300
  • Detection of mutations for risk assessment and prevention 301
  • Impact of biomarkers on management of cancer 301
  • HER-2/neu oncogene as a biomarker for cancer 301
  • L-asparaginase treatment of cancer guided by a biomarker 302
  • Oncogene GOLPH3 as a cancer biomarker 302
  • Predictive biomarkers for cancer 302
  • Sequencing to discover biomarkers to personalize cancer treatment 303
  • VeraTag™ assay system for cancer biomarkers 303
  • Determination of response to therapy 304
  • Biomarker-based assays for predicting response to anticancer therapeutics 304
  • ChemoFx cell culture assay for predicting anticancer drug response 304
  • Ex vivo testing of tumor biopsy for chemotherapy sensitivity 305
  • Genomic approaches to predict response to anticancer agents 305
  • Gene expression patterns to predict response of cancer to therapy 305
  • Genomic analysis of tumor biopsies 306
  • Genotype-dependent efficacy of pathway inhibition in cancer 306
  • Mutation detection at molecular level 306
  • RNA Disruption Assay™ 307
  • Role of genetic variations in susceptibility to anticancer drugs 307
  • Non-genetic factors for variations in response of cancer cells to drugs 307
  • Proteomic analysis of tumor biopsies to predict response to treatment 307
  • Real-time apoptosis monitoring 308
  • Serum nucleosomes as indicators of sensitivity to chemotherapy 308
  • Targeted microbubbles to tumors for monitoring anticancer therapy 309
  • PET imaging for determining response to chemotherapy 309
  • PET imaging with tyrosine kinase inhibitors 310
  • Tissue systems biology approach to personalized management of cancer 310
  • Molecular diagnostics combined with cancer therapeutics 310
  • AmpliChip P53 as companion diagnostic for cancer 310
  • Aptamers for combined diagnosis and therapeutics of cancer 311
  • Combining diagnosis and therapy of metastatic cancer 311
  • Detection and destruction of CTCs with nanoparticles and X-rays 312
  • Monoclonal antibodies for combining diagnosis with therapy of cancer 313
  • Molecular profiling of cancer 313
  • Targeted cancer therapies 313
  • Targeting glycoproteins on cell surface 313
  • Targeting pathways in cancer 313
  • Targeted personalized anticancer medicines in clinical use 314
  • Functional antibody-based therapies 314
  • Personalized cancer vaccines 316
  • Antigen-specific vaccines 316
  • Active immunotherapy based on antigen specific to the tumor 316
  • Tumor-derived vaccines 317
  • FANG vaccine 317
  • MyVax 318
  • OncoVAX 318
  • Tumor cells treated with dinitrophenyl 318
  • Prophage 318
  • Melacine 319
  • Patient-specific cell-based vaccines 319
  • Dendritic cell-based vaccines 319
  • Adoptive cell therapy 321
  • Combination of antiangiogenic agents with ACT 322
  • Genetically targeted T cells for treating B cell malignancies 322
  • Genetic engineering of tumor cells 323
  • Hybrid cell vaccination 323
  • Personalized peptide cancer vaccines 323
  • Current status and future prospects of personalized cancer vaccines 324
  • Personalized radiation therapy 325
  • Use of radiation sensitivity biomarkers to personalized radiotherapy 326
  • Use of imaging to monitor radioimmunotherapy of non-Hodgkin lymphoma 326
  • Role of nanobiotechnology in personalized management of cancer 327
  • Design of future personalized cancer therapies 327
  • Personalized therapy of cancer based on cancer stem cells 328
  • Role of epigenetics in development of personalized cancer therapies 328
  • Selective destruction of cancer cells while sparing normal cells 329
  • Sphingolipids 329
  • Hyperbaric oxygen as adjunct to radiotherapy 330
  • Targeting response to transformation-induced oxidative stress 330
  • Targeting enzymes to prevent proliferation of cancer cells 330
  • Role of oncoproteomics in personalized therapy of cancer 330
  • Cancer tissue proteomics 331
  • Role of sequencing in personalized therapy of cancer 331
  • Pharmacogenomic-based chemotherapy 332
  • Whole genome technology to predict drug resistance 332
  • Anticancer drug selection based on molecular characteristics of tumor 333
  • Testing microsatellite-instability for response to chemotherapy 333
  • Pharmacogenetics of cancer chemotherapy 334
  • CYP 1A2 334
  • Thiopurine methyltransferase 334
  • Dihydropyrimidine dehydrogenase 335
  • UGT1A1 test as guide to irinotecan therapy 335
  • Role of computational models in personalized anticancer therapy 336
  • A computational model of kinetically tailored treatment 336
  • Mathematical modeling of tumor mivroenvironments 337
  • Modeling signaling pathways to reposition anticancer drugs 337
  • Therapy resistance in cancer 337
  • Mechanism of therapy resistance in cancer 338
  • Role of splice variants in resistance to cancer therapy 338
  • Expression of P-glycoprotein gene by tumor 338
  • Overexpression of multidrug resistance gene 338
  • P53 mutations 339
  • Detection of drug resistance 339
  • Anaplastic lymphoma kinase 339
  • Metabolic profiling of cancer 339
  • Management of drug resitance in cancer 340
  • Chemogenomic approach to drug resistance 340
  • Determination of chemotherapy response by topoisomerase levels 340
  • Management of drug resistance in leukemia 340
  • Resistance to vaccines in cancer recurrence after surgery 341
  • Systems biology approach to drug-resistant cancer 341
  • Personalized therapy of cancer metastases 342
  • Personalized management of cancers of various organs 342
  • Personalized management of brain tumors 342
  • Aptamers for selective targeting of tumor initiating cells in GBM 342
  • Bioinformatic approach to personalizing treatment of GBM 343
  • Biosimulation approach to personalizing treatment of brain cancer 343
  • Companion diagnostic for viral gene therapy of brain cancer 343
  • Drug resistance in GBM 344
  • Genetics and genomics of brain cancer 344
  • Glioma Actively Personalized Vaccine Consortium 345
  • Prognosis of glioblastoma multiforme based on its genetic landscape 346
  • Molecular diagnostics for personalized management of brain cancer 346
  • Personalized chemotherapy of brain tumors 348
  • Supratentorial hemispheric diffuse low-grade gliomas 349
  • Personalized therapy of oligodendroglial tumors (OTs) 350
  • Personalized therapy of neuroblastomas 350
  • Personalized therapy of medulloblastomas 351
  • Personalized management of germ cell brain tumors 351
  • Personalized management of meningiomas 352
  • Future prospects of personalized therapy of malignant gliomas 352
  • Personalized management of breast cancer 353
  • Developing personalized drugs for breast cancer 353
  • Gene expression plus conventional predictors of breast cancer 354
  • Her2 testing in breast cancer as a guide to treatment 355
  • HER2/neu-derived peptide vaccine for breast cancer 356
  • Molecular diagnostics in breast cancer 357
  • Monitoring of circulating tumor cells in metastatic breast cancer 359
  • Pharmacogenetics of breast cancer 359
  • Proteomics-based personalized management of breast cancer 360
  • Predicting response to chemotherapy in breast cancer 360
  • Prediction of resistance to chemotherapy in breast cancer 363
  • Prediction of adverse reaction to radiotherapy in breast cancer 364
  • Prediction of recurrence in breast cancer for personalizing therapy 364
  • Prognosistic tests for breast cancer 366
  • Racial factors in the management of breast cancer 368
  • RATHER consortium to study personalized approach to breast cancer 368
  • TAILORx (Trial Assigning Individualized Options for Treatment) 369
  • Tamoxin therapy for ER-positive breast cancer 369
  • Triple negative breast cancer 370
  • Trends and future prospects of breast cancer research 370
  • Understanding tumor diversity in mouse mammary cancer model 372
  • Personalized management of ovarian cancer 372
  • Early diagnosis of ovarian cancer 372
  • Determining response to chemotherapy in ovarian cancer 373
  • Prognosis of ovarian cancer based on CLOVAR 373
  • Recurrent and drug-resistant ovarian cancer 374
  • Pathway targeted therapies for ovarian cancer 375
  • Targeting hematogenous metastasis of ovarian cancer 376
  • Vynfinit ® for platinum-resistant ovarian cancer 377
  • Personalized management of head and neck cancer 377
  • Relevance of biomarkers of HPV-related head and neck cancer 377
  • Personalized management of hematological malignancies 378
  • Personalized management of acute lymphoblastic leukemia 379
  • Personalized management of acute myeloid leukemia 379
  • Personalized management of chronic lymphocytic leukemia 381
  • Personalized management of multiple myeloma 382
  • Personalized management of myelodysplastic syndrome 383
  • Personalized management of lymphomas 384
  • Personalized management B cell lymphomas 384
  • Personalized vaccine for follicular lymphoma 385
  • Companion diagnostic for treatment of lymphoma with Adcentris™ 385
  • Personalized management of hepatocellular carcinoma 386
  • Personalized management of gastrointestinal cancer 386
  • Personalized management of esophageal cancer 386
  • Personalized management of gastric cancer 387
  • Personalized management of colorectal cancer 387
  • Sequencing for personalized management of colorectal cancer 390
  • Systems biology approach to drug resistance in colorectal cancer 391
  • Resistance to targeted EGFR blockade in CRC 392
  • Personalized management of liver cancer 392
  • Personalized management of lung cancer 393
  • Crizotinib for personalized management of NSCLC 393
  • Ceritinib 393
  • EGFR tyrosine kinase inhibitor treatment 393
  • Development of resistance to EGFR inhibitors 395
  • Molecular subtyping of lung cancer 396
  • Personalized therapy of NSCLC based on KIF5B/RET fusion oncogene 396
  • Predicting response of NSCLC to platinum-based therapy 397
  • Proteomics for discovery of metabolic biomarkers of lung cancer 397
  • Role of a new classification system in the management of lung cancer 397
  • Selecting therapy of cancer arising from respiratory papillomatosis 397
  • Testing for response to chemotherapy in lung cancer 398
  • Testing for prognosis of lung cancer 398
  • Testing for recurrence of lung cancer 399
  • Personalized management of malignant melanoma 399
  • Inhibitors of BRAF mutation for metastatic melanoma 399
  • Management of drug-resistant metastatic melanoma 400
  • Vaccine for malignant melanoma based on heat shock protein 400
  • Personalized management of pancreatic cancer 401
  • Biomarkers of pancreatic cancer 401
  • Histone modifications predict treatment response in pancreatic cancer 401
  • Transport properties of pancreatic cancer and gemcitabine delivery 402
  • Personlized management of prostate cancer 402
  • Assessing susceptibility to prostate cancer by genotyping 403
  • Diagnostics for guiding therapy of prostate cancer 403
  • Detection of prostate cancer metastases 404
  • Early detection of cancer recurrence and guiding treatment 404
  • Effects of of lifestyle changes shown by gene expression studies 404
  • Prolaris assay for determining prognosis in prostate cancer 405
  • Personalized peptide vaccine for prostate cancer 405
  • Future of cancer therapy 405
  • Challenges for developing personalized cancer therapies 405
  • Cancer Genome Atlas 406
  • COLTHERES consortium 406
  • Computer and imaging technologies for personalizing cancer treatment 407
  • Genomic Cancer Care Alliance 407
  • Global Cancer Genomics Consortium 407
  • Integrated genome-wide analysis of cancer for personalized therapy 407
  • International Cancer Genome Consortium 408
  • National Cancer Institute of US 409
  • PREDICT Consortium 409
  • Quebec Clinical Research Organization in Cancer 410
  • Companies involved in developing personalized oncology 410

11. Development of Personalized Medicine 413

  • Introduction 413
  • Non-genomic factors in the development of personalized medicine 413
  • Personalized medicine based on circadian rhythms 413
  • Cytomics as a basis for personalized medicine 415
  • Intestinal microflora 415
  • Gut microbiome compared to human genome 415
  • Metabolic interactions of the host and the intestinal microflora 416
  • Role of drug delivery in personalized medicine 416
  • Personalized approach to clinical trials 416
  • Use of Bayesian approach in clinical trials 416
  • Individualzing risks and benefits in clinical trials 417
  • Clinical trials of therapeutics and companion diagnostics 418
  • Players in the development of personalized medicine 418
  • Personalized Medicine Coalition 418
  • European Personalized Medicine Diagnostics Association 419
  • Role of pharmaceutical industry 420
  • Production and distribution of personalized medicines 420
  • Role of biotechnology companies 421
  • Role of life sciences industries 421
  • Role of molecular imaging in personalized medicine 422
  • Molecular imaging for personalized drug development in oncology 422
  • Molecular imaging and CNS drug development 424
  • Companies involved in molecular imaging 425
  • Role of the clinical laboratories 425
  • Role of the US government in personalized medicine 426
  • Department of Health and Human Services and personalized medicine 427
  • Agency for Healthcare Research and Quality 427
  • Comparative effectiveness research 428
  • Role of the US Government agencies in personalized medicine 429
  • NIH's Roadmap Initiative for Medical Research 430
  • NIH and personalized medicine 430
  • NIH collaboration with the FDA 431
  • NIH and Genetic Testing Registry 431
  • National Human Genome Research Institute 431
  • National Institute of General Medical Sciences 431
  • National Institute of Standards and Technology 433
  • Role of the Centers for Disease Control 434
  • Role of academic institutions in the US 434
  • Baylor College of Medicine 434
  • Clinical Proteomics Program of NCI & FDA 435
  • Coriell Personalized Medicine Collaborative™ 435
  • Delaware Valley Personalized Medicine Project 436
  • Duke University Medical Center and genomic medicine 436
  • Evaluation of genetic tests and genomic applications 437
  • Ignite Institute 437
  • Indiana University Institute for Personalized Medicine 437
  • Institute of Medicine's role in personalized medicine 438
  • Jackson Laboratory for Genomic Medicine 439
  • Johns Hopkins Center for Personalized Cancer Medicine Research 439
  • Mayo Clinic's Centers for Individualized Medicine 439
  • Mt. Sinai Medical Center's Personalized Medicine Research Program 440
  • P4 Medicine Institute 440
  • Personalized Medicine Partnership of Florida 440
  • Personalized oncology at Massachusetts General Hospital 441
  • Personalized oncology at Oregon Health & Science University 441
  • Pharmacogenetics Research Network and Knowledge Base 442
  • Southeast Nebraska Cancer Center's Personalized Medicine Network 442
  • Stanford Center for Genomics and Personalized Medicine 442
  • UAB-HudsonAlpha Center for Genomic Medicine 443
  • University of Colorado's Center for Personalized Medicine 443
  • UNC Institute for Pharmacogenomics and Individualized Therapy 443
  • Wisconsin Genomics Initiative 444
  • Role of academic collaborations with companies 444
  • New York Genome Center 444
  • Role of healthcare organizations 445
  • Role of the medical profession 445
  • The American Medical Association and personalized medicine 445
  • Education of the physicians 445
  • Off-label prescribing and personalized medicine 446
  • Medical education 446
  • Role of patients 447
  • Public attitude towards personalized medicine 447
  • Role of genetic banking systems and databases 448
  • Role of biobanks in development of personalized medicine 448
  • UK Biobank 448
  • Biobanking and development of personalized medicine in EU 449
  • CARTaGENE for biobanks in Canada 449
  • Personalized medicine based on PhysioGenomics™ technology 450
  • Role of bioinformatics in development of personalized medicine 450
  • Exploration of disease-gene relationship 452
  • Biosimulation techniques for developing personalized medicine 452
  • Health information management 452
  • Electronic health records 452
  • Cost of EHR and savings on healthcare expenses in the US 453
  • EHRs and genome-wide studies 453
  • Linking patient medical records and genetic information 454
  • Management of personal genomic data 454
  • Use of EHRs for improving safety of new medicines 455
  • Use of EHRs for genetic research 455
  • Use of EHRs for personalized drug discovery and development 456
  • Personalized prognosis of disease 456
  • Integration of technologies for development of personalized medicine 456
  • Global scope of personalized medicine 457
  • Personalized medicine in Canada 457
  • Personalized medicine at Ontario Institute for Cancer Research 457
  • Personalized Medicine Partnership for Cancer in Quebec 459
  • Quebec Center of Excellence in Personalized Medicine 459
  • Personalized medicine in the EU 459
  • UK National Health Service and medical genetics 460
  • Personalized medicine in Germany 461
  • Personalized medicine in Israel 461
  • Personalized medicine in the developing countries 462
  • Advantages and limitations of personalized medicine 462
  • Limitations of personalized medicine 463
  • Future of personalized medicine 464
  • Ongoing genomic projects 464
  • Understanding the genetic basis of diseases 465
  • Personal Genome Project 465
  • Genome-wide association studies 466
  • The 1000 Genomes Project 467
  • Genomics of aging in a genetically homogeneous population 467
  • Translational science and personalized medicine 467
  • Translation of genomic research into genetic testing for healthcare 468
  • Long-term behavioral effects of personal genetic testing 468
  • Personalized predictive medicine 469
  • Connected health and personalized medicine 470
  • Opportunities and challenges 470
  • Prospects and limitations of genetic testing 470
  • Genetic testing and concerns about equality of healthcare 471
  • Pharmacotyping 471
  • Comparative-effectiveness research and personalized medicine 472
  • Medicine in the year 2018 472
  • Concluding remarks about the future of personalized medicine 473

12. Ethical, Legal and Regulatory Aspects of Personalized Medicine 475

  • Introduction to ethical issues 475
  • Ethical issues of pharmacogenetics 475
  • Ethical aspects of genetic information 475
  • Ethical issues of whole genome analysis 475
  • Ethical aspects of direct-to-consumer genetic services 476
  • Privacy issues in personalized medicine 477
  • Genetic Information Nondiscrimination Act in the US 478
  • Genotype-specific clinical trials 478
  • Social issues in personalized medicine 478
  • Race and personalized medicine 479
  • Legal issues of personalized medicine 480
  • Gene patents and personalized medicine 481
  • Regulatory aspects 481
  • CLSI guideline for the use of RNA controls in gene expression assays 482
  • MicroArray Quality Control Project 482
  • Regulatory aspects of pharmacogenetics 483
  • Regulation of direct-to-consumer genetic testing 484
  • Need for regulatory oversight of DTC 484
  • FDA and pharmacogenomics 486
  • FDA guidance for pharmacogenomic data submissions 487
  • Joint guidelines of the FDA and EU regulators for pharmacogenomics 488
  • Pharmacogenomic/pharmacogenetic information in drug labels 488
  • FDA guidelines for pharmacogenomics-based dosing 489
  • FDA and validation of biomarkers 489
  • FDA and predictive medicine 490
  • FDA regulation of multivariate index assays 490
  • Evaluation of companion diagnostics/therapeutic 492

13. Commercial Aspects of Personalized Medicine 495

  • Introduction 495
  • Perceived financial concerns 495
  • Personalized medicine and orphan drug syndrome 495
  • Commercial aspects of pharmacogenomics 495
  • Cost of DNA testing 495
  • Cost of sequencing the human genome 496
  • Cost of genotyping 498
  • Cost of pharmacogenomics-based clinical trials 499
  • Business development of pharmacogenomic companies 499
  • Cost of personalized healthcare 500
  • The rising healthcare costs in the US 500
  • Genetic testing and cost of healthcare 500
  • Reducing healthcare costs by combining diagnostics with therapeutics 501
  • Cost-effectiveness of pharmacogenetic testing 501
  • Cost-effectiveness of CYP genotyping-based pharmacotherapy 502
  • Cost effectiveness of HIV genotyping in treatment of AIDS 502
  • Cost-effectiveness of warfarin pharmacogenomics 503
  • Cost-benefit analysis of KRAS and BRAF screening in CRC 503
  • Lowering the high costs of cancer chemotherapy 504
  • Overall impact of personalized medicine on healthcare 504
  • Drivers for the development of personalized medicine 504
  • Evolution of medicine as a driver for personalized therapy markets 505
  • Collaboration between the industry and the academia 506
  • Personalized medicine and drug markets 506
  • Segmentation of therapeutic drug markets 506
  • Reasons for increase of market values of personalized medicines 507
  • Growth of markets relevant to personalized medicine 507
  • Biochips 508
  • Pharmacogenetics 508
  • Pharmacogenomics 508
  • Pharmacoproteomics 508
  • Point-of-Care 508
  • SNP market 508
  • Markets for personalized medicines according to therapeutic areas 509
  • Market for personalized cancer therapy 509
  • Markets for personalized medicines according to geographical regions 509
  • Market opportunities for personalization of medicine 510
  • Impact of personalized medicine on other industries 510
  • Strategies for developing and marketing personalized medicine 511
  • Education of the public 511
  • Role of the Internet in development of personalized medicine 512
  • Marketing companion diagnostics for personalized medicine 512

14. References 515

Tables

  • Table 1-1: Selected terms relevant to the concept of personalized medicine 23
  • Table 1-2: Landmarks in the historical development of personalized medicine 24
  • Table 1-3: Genetic variations in the human genome 29
  • Table 2-1: Molecular diagnostic technologies used for personalized medicine 51
  • Table 2-2: Applications of biochip technology relevant to personalized medicine 71
  • Table 2-3: Companies developing haplotying technology 86
  • Table 2-4: Technologies for SNP analysis 86
  • Table 2-5: A sampling of companies involved in technologies for SNP genotyping 95
  • Table 2-6: Comparison of proteomic and genomic approaches in personalized medicine 103
  • Table 2-7: Selected methods for gene expression profiling 104
  • Table 2-8: A selection of companies with gene expression technologies 109
  • Table 2-9: Drugs requiring biomarker/companion diagnostic information in the label 112
  • Table 2-10: Companies involved in companion diagnostics 113
  • Table 2-11: Applications of point-of-care diagnosis 115
  • Table 2-12: Companies developing point-of-care diagnostic tests 116
  • Table 2-13: Companies offering genetic screening tests directly to consumers 120
  • Table 3-1: Pharmacogenetic vs. pharmacogenomic studies 126
  • Table 3-2: Enzymes relevant to drug metabolism 128
  • Table 3-3: Examples of mutation of the enzyme CYP450 129
  • Table 3-4: Frequency distribution of drugs metabolized by major isoforms of CYP450. 129
  • Table 3-5: Commonly prescribed medications, which are metabolized by CYP2D6 129
  • Table 3-6: Polymorphisms in drug target genes that can influence drug response 135
  • Table 3-7: Effect of genetic polymorphisms on disease response to drugs 136
  • Table 3-8: Examples of genetically determined adverse reactions to drugs 139
  • Table 3-9: Examples of genotyping and phenotyping in some diseases 147
  • Table 3-10: Companies with novel molecular toxicology technology 149
  • Table 3-11: Pharmacogenomic biomarkers in drug labeling 152
  • Table 4-1: Role of pharmacogenomics in variable therapy targets 161
  • Table 4-2: Role of pharmacogenomics in clinical trials 164
  • Table 4-3: Examples of pharmacogenomics-based clinical studies 165
  • Table 4-4: Tumor suppressor genes, their chromosomal location, function and associated tumors. 168
  • Table 4-5: Gene polymorphisms relevant to cardiovascular disease management 169
  • Table 4-6: Companies involved in cardiovascular genomics 171
  • Table 4-7: A sampling of companies involved in neuropharmacogenomics 173
  • Table 9-1: Important therapeutic areas for personalized medicine 201
  • Table 9-2: Enzymes that metabolize antipsychotics 215
  • Table 9-3: Enzymes that metabolize antidepressants 216
  • Table 9-4: Biomarkers of epilepsy 223
  • Table 9-5: Gene expression as biomarker of response to IFN-β in multiple sclerosis 236
  • Table 9-6: P450 isoforms in the metabolism of drugs used in the management of pain 238
  • Table 9-7: Personalized management of neuropathic pain based on mechanism 242
  • Table 9-8: Genes that cause cardiovascular diseases 244
  • Table 9-9: Genetic influences on pharmacotherapy of alcoholism 280
  • Table 10-1: Factors that drive the development of personalized therapy in cancer 287
  • Table 10-2: Impact of molecular diagnostics on the management of cancer 289
  • Table 10-3: Marketed anticancer personalized medicines 314
  • Table 10-4: Clinical trials of personalized cancer vaccines 324
  • Table 10-5: Selected companies involved in developing personalized oncology 410
  • Table 11-1: Players in the development of personalized medicine 418
  • Table 11-2: Members of the Personalized Medicine Coalition 419
  • Table 11-3: Biobanks relevant to personalized medicine 448
  • Table 11-4: Role of bioinformatics in the development of personalized medicine 450
  • Table 11-5: Advantages of personalized medicine for the biopharmaceutical industry 462
  • Table 11-6: Advantages of personalized medicine for the patients 463
  • Table 11-7: Advantage of personalized medicine for the physicians 463
  • Table 11-8: Advantage of personalized medicine for the healthcare providers 463
  • Table 11-9: Limitations of personalized medicine 463
  • Table 11-10: Methods of translational science that are relvant to personalized medicine 468
  • Table 11-11: Companies involved in predictive healthcare 469
  • Table 12-1: Drugs with genetic information in their labels 488
  • Table 13-1: Drivers for the development of personalized medicine 504
  • Table 13-2: Growth of markets relevant to personalized medicine 2013-2023 507
  • Table 13-3: Markets for personalized medicine according to therapeutic area 2013-2023 509
  • Table 13-4: Markets for personalized medicine in major regions 2013-2023 509
  • Table 13-5: Lack of efficacy in current therapy 510
  • Table 13-6: Impact of personalized medicine on other industries 510
  • Table 13-7: Strategies to develop personalized medicine 511
  • Table 13-8: Role of the Internet in development of personalized medicine 512

Figures

  • Figure 1-1: Relation of personalized medicine to other technologies 39
  • Figure 1-2: Relation of systems pharmacology to personalized medicine 45
  • Figure 2-1: Role of sequencing in personalized medicine 69
  • Figure 2-2: Role of biochip/microarray technology in personalized medicine 71
  • Figure 2-3: Application of biochips/microarrays in personalized therapy 72
  • Figure 2-4: Affymetrix GeneChip technology 73
  • Figure 2-5: Role of CYP450 genotyping in development of personalized medicine 74
  • Figure 2-6: Role of SNPs in personalized medicine 82
  • Figure 2-7: A scheme of integrated healthcare and personalized medicine 121
  • Figure 3-1: Pharmacogenetics as a link between genotype and phenotype 125
  • Figure 3-2: Role of pharmacogenetic technologies in personalized medicine 126
  • Figure 4-1: Impact of new technologies at various stages of the drug discovery process 163
  • Figure 4-2: Steps in the application of pharmacogenomics in clinical trials 165
  • Figure 7-1: Role RNAi in development of personalized medicine 192
  • Figure 9-1: Workflow of genotypic resistance analysis for personalized HIV therapy 207
  • Figure 9-2: Scheme of iPSCs for personalized cell therapy of Parkinson disease 222
  • Figure 9-3: Algorithm for personalized management of epilepsy 229
  • Figure 9-4: Essential components of personalized management of pain 237
  • Figure 9-5: Genetic and non-genetic factors affecting efficacy and side effects of opioids 239
  • Figure 9-6: An algorithm for personalized management of pain 242
  • Figure 9-7: A scheme of personalized approach to management of hypertension 256
  • Figure 10-1: Relationships of technologies for personalized management of cancer 288
  • Figure 11-1: Integration of technologies for the development of personalized medicine 456
  • Figure 13-1: Cost of sequencing per genome 498
  • Figure 13-2: Evolution of personalized medicine as a market driver 505

Part II

14. Companies Involved in Developing Personalized Medicine 5

Introduction 5 Profiles 5 Collaborations 205

Tables

  • Table 14-1: Top five companies involved in personalized medicine 5
  • Table 14-2: Selected collaborations of companies in personalized medicine 205
Show More
Pricing