Personalized Medicine - Scientific & Commercial Aspects

Table of Contents

Part I: Technologies & Applications

Executive Summary

1. Basic Aspects

• Definition of personalized medicine
• History of medical concepts relevant to personalized medicine 
• Evolution of modern personalized medicine 
• Molecular biological basis of personalized medicine
• The human genome 
• ENCODE  
• Chromosomes 
• Genes 
• The genetic code 
• Gene expression 
• DNA sequences and structure
• Genetic variations in the human genome  
• Single nucleotide polymorphisms
• Copy number variations in the human genome
• Insertions and deletions in the human genome
• Large scale variation in human genome 
• Structural variations in the human genome  
• Mapping and sequencing of structural variation from human genomes
• 1000 Genomes Project  
• Role of DNA sequencing in the development of personalized medicine
• Human Variome Project
• Interconnected genetic and genomic patterns in human diseases
• 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
• Genetic databases
• Clinical Genomic Database
• Genetic epidemiology
• Limitations of medical genetics 
• 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
• 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
• Cancer in dogs  
• Reclassification of diseases
• Translational science and personalized medicine
• Genome to phenome translation  
• Personalization of multimodal therapies  

2. Molecular Diagnostics in Personalized Medicine

• Introduction
• Molecular diagnostic technologies 
• PCR-based methods 
• DirectLinear™ Analysis  
• Denaturing high-performance liquid chromatography
• Multiplex Allele-Specific Diagnostic Assay
• Representational oligonucleotide microarray analysis
• Restriction fragment length polymorphism (RFLP)
• Real-time PCR for detection of CNVs
• Non-PCR methods  
• Arrayed primer extension (APEX)
• Enzymatic Mutation Detection (EMD) 
• DNA sequencing
• Sanger-sequencing technology 
• ABI PRISM® 310 Genetic Analyzer  
• High-throughput paired end transcriptome sequencing  
• Emerging sequencing technologies 
• 4300 DNA analyzer 
• Apollo 100 
• Cyclic array sequencing
• CEQ™ 8000  
• DeepCAGE sequencing 
• Electron microscope-based DNA sequencing
• IBS sequencing technology
• Illumina’s sequencing technology
• Ion Torrent's sequencing technology
• Life Technologies 3500 series Genetic Analyzer
• MegaBACE 500
• Microdroplet-based PCR for large-scale targeted sequencing
• Multiplex amplification of human DNA sequences  
• Nanoscale sequencing 
• Next generation sequencing based on Lightning Terminators  
• Polonator sequencer  
• RainStorm™ microdroplet technology  
• Roche GL-FLEX sequencing
• Sequential DEXAS
• SOLiD technology  
• Sequencing by hybridization 
• Whole genome sequencing
• Bioinformatic tools for analysis of genomic sequencing data 
• Clinical Genomicist Workspace for managing NGS-based clinical tests  
• Detection of single molecules in real time
• Direct observation of nucleotide incorporation  
• Molecular Combing
• Nanopore sequencing
• DNA sequence by use of nanoparticles
• Zero-mode waveguide nanostructure arrays
• Future prospects of sequencing
• Role of DNA sequencing in development of personalized medicine 
• Role of RNA sequencing in development of personalized medicine 
• Biochips and microarrays
• Role of biochip/microarray technology in personalized medicine 
• Applications of biochip/microarray technology in personalized medicine
• Standardizing the microarrays
• Biochip technologies 
• GeneChip
• AmpliChip CYP450
• Microfluidics  
• Lab-on-a-chip 
• Micronics' microfluidic technology
• LabCD
• Microfluidic automated DNA analysis using PCR
• Integrated microfluidic bioassay chip 
• 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
• ProteinChip  
• LabChip for protein analysis 
• TRINECTIN proteome chip  
• Protein expression microarrays 
• Microfluidic devices for proteomics-based diagnostics
• New developments in protein biochips/microarrays 
• Protein biochips/microarrays for personalized medicine  
• SNP genotyping 
• Genotyping and haplotyping
• Haplotype Specific Extraction
• Computation of haplotypes
• HapMap project
• Haplotyping for whole genome sequencing 
• Predictingdrug response with HapMap
• Companies developing haplotyping technology
• Technologies for SNP analysis  
• Biochip and microarray-based detection of SNPs
• SNP genotyping by MassARRAY
• BeadArray technology
• SNP-IT primer-extension technology 
• Use of NanoChip for 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  
• Companies involved in developing technologies/products for SNP analysis  
• 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
• Proteomic strategies for biomarker identification  
• Proteomic technologies for detection of biomarkers in body fluids
• Protein patterns 
• Layered Gene Scanning
• Comparison of proteomic and genomic approaches in personalized medicine 
• Role of nanobiotechnology in molecular diagnostics  
• Cantilevers for personalized medical diagnostics  
• Role of biomarkers in personalized medicine
• Role of biosensors in personalized medicine  
• Biomarkers for diagnostics
• Biomarkers for drug development  
• 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  
• Companies involved in gene expression analysis  
• 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  
• Companies developing point-of-care diagnostic technologies
• Point-of-care diagnosis of infections 
• Advantages versus disadvantages of point-of-care diagnosis
• Future prospects 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
• Screening  
• Disease prediction 
• Early diagnosis 
• Prevention
• Therapy based on molecular diagnosis 
• Monitoring of therapy  
• Advantages and limitations of integrated healthcare
• Commercially available systems for integrated healthcare
• Future of molecular diagnostics in personalized medicine

3. 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
• CYP450  
• CYP2D6 inhibition by selective serotonin reuptake inhibitors
• CYP2D6 genotype and codeine pharmacokinetics
• Cytochrome P450 polymorphisms and response to clopidogrel  
• Lansoprazole and cytochrome P450 
• Glucose-6-phosphate dehydrogenase
• Pharmacogenetics of phase II metabolism
• N-Acetyltransferase
• Uridine diphosphate-glucuronosyltransferase  
• Measurement of CYP isoforms 
• Polymorphism of drug transporters
• Genetic variation in drug targets
• Polymorphisms of kinase genes
• Effect of genetic polymorphisms on disease response to drugs  
• Ethnic differences in drug metabolism
• Gender differences in pharmacogenetics
• Role of pharmacogenetics in drug safety
• Adverse drug reactions
• Adverse drug reactions in children
• Adverse drug reactions related to toxicity of chemotherapy  
• Genetically determined adverse drug reactions 
• Malignant hyperthermia 
• Pharmacogenetics of clozapine-induced agranulocytosis 
• Role of pharmacogenetics in warfarin therapy
• Role of pharmacogenetics in antiplatelet therapy
• Role of pharmacogenetics in carbamazepine therapy 
• Role of pharmacogenetics in statin therapy
• FDA consortium linking genetic biomarkers to serious adverse events 
• Therapeutic drug monitoring, phenotyping, and genotyping  
• Applications of therapeutic drug monitoring
• Phenotyping 
• Genotyping
• Genotyping vs phenotyping  
• Phenomics  
• Limitations of genotype-phenotype association studies
• Molecular toxicology in relation to personalized medicines
• Toxicogenomics  
• Biomarkers of drug toxicity  
• Drug-induced mitochondrial toxicity  
• Companies involved in molecular toxicology 
• Gene expression studies  
• Pharmacogenetics in clinical trials  
• Postmarketing pharmacogenetics 
• Clinical implications of pharmacogenetics
• Application of CYP450 genotyping in clinical practice 
• Genotype-based drug dose adjustment  
• Pharmacogenomic biomarker information in drug labels 
• Standardized terminology for clinical pharmacogenetic test results
• Use of pharmacogenetics in clinical pharmacology
• Application of CYP2C19 pharmacogenetics for personalized medicine
• Genotyping for identifying responders to sulfasalazine
• HLA alleles associated with lumiracoxib-related liver injury  
• Pharmacogenetic basis of thiopurine toxicity  
• Tranilast-induced hyperbilirubinemia due to gene polymorphism 
• Linking pharmacogenetics with pharmacovigilance 
• Genetic susceptibility to ADRs
• Linking genetic testing to postmarketing ADR surveillance 
• Recommendations for the clinical use of pharmacogenetics 
• Limitations of pharmacogenetics 
• Pharmacoepigenomics vs pharmacogenetics in drug safety  
• Future role of pharmacogenetics in personalized medicine 

4. 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
• Oncogenes
• Tumor suppressor genes  
• Cardiogenomics 
• Neuropharmacogenomics  
• Pharmacogenomics of Alzheimer's disease
• Pharmacogenomics of depression  
• Pharmacogenomics of bipolar disorder 
• Pharmacogenomics of schizophrenia  
• Companies involved in neurogenomics-based drug discovery
• Current state and future of pharmacogenomics

5. 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
• Applications of pharmacoproteomics in personalized medicine

6. Role of Metabolomics in Personalized Medicine

• Metabolomics and metabonomics  
• Metabolomics bridges the gap between genotype and phenotype
• Metabolomics, biomarkers and personalized medicine  
• Metabolomic technologies
• Urinary profiling by capillary electrophoresis
• Lipid profiling  
• Role of metabolomics in biomarker identification and pattern recognition
• Pharmacometabonomics
• Metabonomic technologies for toxicology studies  
• Metabonomics/metabolomics and personalized nutrition  
• Metabolomics for personalized medicine 

7. Personalized Biological Therapies

• Introduction  
• Recombinant human proteins
• Therapeutic monoclonal antibodies 
• Cell therapy 
• Autologous tissue and cell transplants
• Stem cells 
• iPSCs for personalized cell therapy
• Role of stem cells derived from unfertilized embryos 
• 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
• Stem cell-based personalized gene therapy for cancer
• Personalized vaccines
• Personalized vaccines for viral diseases  
• Personalized cancer vaccines
• Antisense therapy  
• RNA interference  
• MicroRNAs  

8. Personalized complementary & Alternative Therapies  

• Introduction  
• Ayurveda as a personalized healthcare system
• Taditional Chinese medicine  
• Personalized acupuncture therapy
• Personalized hyperbaric oxygen therapy 
• Personalized nutrition.
• Nutrigenomics
• Evolutionary basis of nutrigenomics  
• Genomics of vitamin D and calcium supplementation 
• Nutrigenomics and functional foods 
• Nutrigenomics and personalized medicine  
• Nutriproteomics  
• Nutrigenetics and personalized medicine
• Personalized diet prescription
• Personalized nutrition and aging 
• Personalized diet for diabetics
• Role of systems medicine in personalized nutrition 
• Companies involved 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  

9. Personalized Medicine in Major Therapeutic Areas 

• Introduction  
• Personalized management of infections
• Genetic susceptibility to infections 
• Personalized use of antibiotics 
• Personalized management of sepsis 
• Role of nanobiotechnology in personalized management of infections
• Personalized management of viral infections 
• Genomic epidemiology of viral diseases
• Management of HIV
• CD4 counts as a guide to drug therapy for AIDS
• Drug-resistance in HIV
• Genetics of human susceptibility to HIV infection
• Measurement of Replication Capacity
• Personalized vaccine for HIV
• Prevention of adverse reactions to antiviral drugs 
• Pharmacogenetics and HIV drug safety  
• Pharmacogenomics of antiretroviral agents
• Role of diagnostic testing in management of HIV
• Role of genetic variations in susceptibility to HIV-1
• Role of personalized HIV therapy in controlling drug resistance
• PhenoSense® to test HIV drug resistance  
• Sequencing for detecting mutations to personalize HIV therapy
• Personalized treatment of hepatitis B
• Personalized treatment of hepatitis C
• Responders vs non-responders to treatment for hepatitis C  
• Drug resistance in hepatitis C 
• Challenges for personalized management of hepatitis C 
• Personalized management of COVID-19  
• Molecular diagnosis of COVID-19  
• Genomics of coronaviruses 
• Genetic susceptibility for severity of COVID-19 
• Risk factors for cardiac complications of COVID-19  
• Strategies for developing therapies for COVID-19 
• Antivirals for COVID-19 
• Cell/gene therapy for COVID-19 
• Personalized approach to passive antibody therapy for COVID-19
• Personalized vaccines for COVID-19  
• Personalized management of tuberculosis 
• Personalized management of fungal infections
• 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 
• Role of protein sFRP3 in predicting response to antidepressants
• Treatment resistant depression
• Vilazodone with a test for personalized treatment of depression
• Personalized management of alcohol use disorder
• Personalized management of autism spectrum disorders 
• Neurological disorders 
• Introduction to personalized neurology 
• 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
• Wearable devices for personalized neurology  
• Role of neuroinformatics in personalized neurology
• Personalized management of Alzheimer's disease
• Personalized management of Parkinson's disease
• Atremorine as personalized dopaminergic therapy for PD
• Brain imaging for diagnosis of neurodegenerative parkinsonism
• Direct-to-consumer genetic testing in PD 
• Disease modification in PD 
• Discovery of subgroup-selective drug targets in PD
• Personalized cell therapy for PD
• Pharmacogenetics of PD
• Use of wearable sensors to monitor PD response to levodopa therapy 
• Personalized selection of targets for deep brain stimulation  
• Personalized management of Huntington disease
• Personalized management of amyotrophic lateral sclerosis
• Personalized management of epilepsy
• Adverse effects of AEDs 
• An algorithm for personalized management of epilepsy
• Biomarkers of epilepsy
• Changes in seizure evolution with circadian timescale  
• Drug resistance in epilepsy
• Genetics/genomics of epilepsy  
• Pharmacogenomics of epilepsy
• Rasmussen’s encephalitis
• Selection of the right AED
• Status epilepticus.
• Future of management of epilepsy
• Personalized management of migraine
• Individualization of use of triptans for migraine  
• Multitarget therapeutics for personalized treatment of headache 
• Personalized strategy for prevention of migraine attacks  
• Personalized management of intracranial aneurysms
• Personalized management of cerebral vasospasm following SAH 
• Personalized management of stroke 
• Biomarkers of stroke 
• Management of a patient with carotid stenosis a risk for stroke
• Anticoagulation for stroke prevention
• Management of acute ischemic stroke 
• Application of proteomics for personalizing stroke management
• Brain imaging for personalized management of stroke
• Deep learning for prediction of final ischemic stroke lesion from MRI
• Intravenous thrombolysis and revascularization in acute stroke
• Personalized management of intracerebral hemorrhage 
• Revascularization procedures in chronic post-stroke stage 
• Personalized cell therapy for management of stroke
• Management of stroke according to stage  
• Personalized treatment of multiple sclerosis
• Autologous bone marrow stem cell therapy for multiple sclerosis  
• Fusokine method of personalized cell therapy of multiple sclerosis
• Immunopathological patterns of demyelination for assessing therapy
• Personalizing mitoxantrone therapy of multiple sclerosis  
• Pharmacogenomics of IFN-β therapy in multiple sclerosis
• Personalizing therapy of MS by use of biomarkers 
• Preclinical detection of multiple sclerosis in children
• Predictive models of individual treatment response in MS
• T cell-based personalized vaccine for MS
• Targeting MS therapy to cell type of lesion
• Personalized management of traumatic brain injury
• Biomarkers of TBI 
• Comparative effectiveness research for management of TBI
• CT scores for prognosis and risk stratification of TBI
• Management of cerebral edema/raised intracranial pressure in TBI 
• Personalized management of myasthenia gravis  
• Personalized management of tinnitus
• Personalized management of pain  
• Genetic factors in response to pain
• Genetic mutations with loss of pain 
• Genetic mutations and painful conditions 
• Mechanism-specific management of pain 
• Gene expression biomarkers for personalizing pain management  
• Pharmacogenetics/pharmacogenomics of pain
• Personalized management of pain with opioids 
• Personalized opioid therapy for noncancer pain 
• Pharmacogenetics of NSAIDs
• Mechanism-specific management of pain 
• Preoperative testing to tailor postoperative analgesic requirements 
• Personalized analgesics.
• Prediction of response to an analgesic by in vitro iPSC based testing
• Signature of pain on brain imaging
• Concluding remarks on personalized management of pain
• Personalized management of sleep disorders 
• Personalized therapy of insomnia  
• Future of personalized neurology 
• Personalized management of ophthalmic disorders 
• Proteomics-based personalized management of uveitis
• Combining cell and gene therapies for retinal disorders
• Cardiovascular disorders 
• Role of diagnostics in personalized management of cardiovascular disease  
• Cardiovascular disorders with a genetic component
• Gene mutations associated with risk of coronary heart disease
• Gene variant as a risk factor for sudden cardiac death
• KIF6 gene test as a guide to management of heart disease  
• NGS sequencing for management of cardiovascular disorders 
• Personalized antiplatelet therapy after PCI
• 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 
• Clinical biomarkers  
• Laboratory biomarkers
• Pharmacogenomics of cardiovascular disorders
• Nanotechnology-based personalized therapy of cardiovascular diseases  
• Personalized management of chronic myocardial ischemia
• Management of chronic angina pectoris
• Inflammation as a target for therapy of myocardial ischemia
• Personalized management of myocardial infarction  
• Management of heart failure
• β-blockers  
• Bucindolol  
• BiDil  
• Cell therapy for cardiac repair 
• Management of atrial fibrillation..
• Treatment targets based on genetic variants  
• Selection of personalized therapy for AF
• Management of hypertension
• Adjusting therapy of hypertension to fluctuations of blood pressure
• Choice of drugs for hypertension 
• Control of blood pressure with vagal nerve stimulation
• Correction of causes and risk factors of hypertension  
• Genes and hypertension  
• Guideline for management of HPN
• Improving management of HPN by targeting new pathways
• Individualized therapy of HPN based on risk factors of heart disease
• Personalized management of hypertensive patients with diabetes
• Personalized management of hypertensive patients with albuminuria
• Personalized management of hypertension in the elderly
• Personalized management of hypertension in women  
• Pharmacogenomics of diuretic drugs
• Pharmacogenomics of ACE inhibitors
• Prediction of antihypertensive activity of rostafuroxin  
• Role of pharmacogenetics in management of hypertension 
• Scheme for management of hypertension by personalized approach  
• Personalized lipid-lowering therapies  
• NIR spectroscopy of plaques to guide cholesterol-lowering therapy 
• Polymorphisms in genes involved in cholesterol metabolism
• Role of eNOS gene polymorphisms
• Prediction of response to statins 
• Personalized management of women with hyperlipidemia
• Therapeutic alternatives in patients with statin intolerance 
• Treatment of familial hypercholesterolemia
• PCSK9 inhibitors
• Concluding remarks on the personalized cholesterol management
• Thrombotic disorders
• Factor V Leiden mutation
• Anticoagulant therapy
• Antiplatelet therapy
• 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  
• Personalized management of pulmonary disorders 
• Role of genetic ancestory in lung function 
• Targeted drug delivery for personalized management of pulmonary disorders
• Personalized therapy of asthma
• Asthma phenotyping for improving therapeutic precision
• Biomarkers for predicting response to corticosteroid therapy
• Genetic polymorphism and response to β2-adrenergic agonists
• Genotyping in asthma
• IgE as guide to dosing of omalizumab for asthma 
• Lebrikizumab for personalised treatment of asthma
• Personalized management of chronic obstructive pulmonary disease  
• Biomarker-guided treatment of COPD
• Molecular phenotype-based treatment of COPD  
• Personalized management of idiopathic pulmonary fibrosis.
• Personalized management of skin disorders  
• Genetic testing for personalized skin care 
• Management of hair loss based on genetic testing
• Personalized urology
• Personalized approaches in immunology 
• Immunological tests in personalized medicine..
• Antibody profiles
• Role of Mannose-binding lectin testing in personalized medicine 
• Pharmacogenetics and pharmacogenomics of immunosuppressive agents 
• Personalized management of patients with lupus erythematosus.
• Personalized therapy of rheumatoid arthritis
• Biomarkers and diagnostics for personalizing therapy of rheumatoid arthritis  
• DIATSTAT™ anti-cyclic citrullinated peptides in 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 management of obesity
• Basics of obesity  
• Genetics of obesity as a basis for personalized management
• Limitations of personalized approach to management of obesity
• Personalized management of diabetes  
• Biomarkers in the management of diabetes
• Closed loop control of type1 DM
• Personalized prediction of postprandial glycemic response.
• Personalized management of monogenic diabetes 
• Selection from multiple options for treatment of T2DM
• Stratification of diabetes into 5 subgroups and personalized medicine.
• Management of genetic disorders  
• Personalized treatment of cystic fibrosis
• Personalized management of Prader-Willi syndrome
• 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  
• Personalized approaches to improve organ transplantation  
• Personalization of kidney transplantation
• Cell-based bioengineered kidney transplant
• Personalization of cardiac transplantation
• Cell-based regeneration of heart for personalized transplantation 
• Prediction of rejection for personalizig anti-rejection treatment  
• Personalized immunosuppressant therapy in organ transplants  
• Role of immunological biomarkers in monitoring grafted patients 
• 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
• Antidepressant therapy for smoking cessation
• DNA methylation-based test for monitoring smoking 
• Effectiveness of nicotine patches in relation to genotype  
• Sex differences in smoking as response to stress
• Personalized geriatrics  
• Chronological vs 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
• Genes and chronic kidney disease
• MicroRNAs and chronic kidney disease 
• Metabolomics and chronic kidney disease 
• TGF-β1 as a target for therapy of chronic kidney disease
• Proteomics and chronic kidney disease  
• Personalized management of renal disease associated with hypertension
• ACE inhibitors as renoprotective agents in hypertension
• Gene associated with end-stage renal disease and hypertension 
• Personalized approach to type I primary hyperoxaluria
• Personalized gynecology 
• Female sexual dysfunction
• Hormone replacement therapy in women 
• 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  
• Development of individualized biological therapies for rare diseases  
• Personalized management of DNA repair disorders 
• Personalized preventive medicine
• Personalized surgery

10. Personalized Therapy of Cancer

• Introduction  
• Epidemiology of cancer
• Development of personalized therapy in cancer 
• Molecular biology of cancer as basis for personalized management
• Cancer epigenetics/epigenomics and personalized therapy 
• Cell division and mitotic spindles 
• Chromosomes and cancer
• Chromosomal instability 
• Extrachromosomal DNA and cancer 
• DNA damage, repair and cancer
• Gene mutations and cancer  
• Telomeres and cancer 
• 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 on 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  
• Gene expression profiling in hematological cancers
• Gene expression profiling in prostate cancer 
• Gene expression profiles predict chromosomal instability in tumors 
• OnkoMatch tumor genotyping 
• Synthetic lethality
• GPS Cancer test 
• Liquid biopsy 
• Targeted digital sequencing  
• Modulation of CYP450 activity for cancer therapy
• NanoFlares for detection of CTCs 
• Pathway-based analysis of cancer  
• Conversion of gene-level information into pathway-level information
• Personalized therapies based on oncogenic pathways signatures 
• Quantum dot-based test for DNA methylation  
• Role of molecular imaging in personalized therapy of cancer
• Functional diffusion MRI 
• FDG-PET/CT for personalizing cancer treatment  
• Image-guided personalized drug delivery in cancer
• Optoacoustic imaging and nanoparticles in cancer management 
• Tumor imaging and elimination by targeted gallium corrole  
• Future of molecular imaging in management 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 
• 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 
• Gene expression patterns to predict response of cancer to therapy 
• Genetic therapy of cancer
• Genomic analysis of tumor biopsies 
• Genotype-dependent efficacy of pathway inhibition in cancer 
• Mutation detection at molecular level
• Predicting response to checkpoint inhibitors 
• RNA Disruption Assay™ 
• 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 
• PET imaging with tyrosine kinase inhibitors
• 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 destruction 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
• Immunotherapy of cancer
• Monoclonal antibodies for personalized management of cancer  
• Targeted MAb-based immune therapy of cancer 
• MAbs targeted to alpha fetaprotein receptor 
• MAbs targeted to tumor blood vessels 
• MAbs that selectively target cancer 
• Velociximab
• MAbs for immune activation  
• Functional MAb-based therapies
• Immunotherapy of dormant cancer
• Combined use of MAbs and cytokines
• Antibody-drug conjugates for personalized therapy of cancer
• Combining diagnostics with therapeutics based on MAbs 
• Radiolabeled antibodies for detection and targeted therapy of cancer
• Cancer immunotherapy based on suppression of enzymes
• Personalized cancer vaccines..
• Antigen-specific vaccines  
• Active immunotherapy based on antigen specific to the tumor  
• Tumor-derived vaccines
• FANG vaccine
• MyVax 
• OncoVAX 
• Tumor cells treated with dinitrophenyl 
• Prophage 
• Melacine
• Patient-specific cell-based vaccines
• Dendritic cell-based vaccines
• Adoptive cell therapy
• Combination of antiangiogenic agents with ACT  
• Genetically targeted T cells for treating B cell malignancies  
• Genetic engineering of tumor cells
• Hybrid cell vaccination
• Personalized peptide cancer vaccines 
• Targeting core mutations in cancer
• Current status and future of personalized cancer vaccines
• 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..
• Role of nanobiotechnology in personalized management of cancer 
• 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 development of personalized cancer therapies  
• Cancer epigenetics and immunotherapy
• Selective destruction of cancer cells while sparing normal cells  
• Sphingolipids  
• Hyperbaric oxygen as adjunct to radiotherapy
• Targeting response to transformation-induced oxidative stress
• Targeting enzymes to prevent proliferation of cancer 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 
• LC-MS/MS proteomics as a companion diagnostic 
• Personalized cancer therapy based on targeted proteomics  
• 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 
• CYP 1A2
• 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  
• Cancer stem cells and radioresistance 
• Expression of P-glycoprotein gene by tumor 
• Overexpression of multidrug resistance gene  
• P53 mutations
• Role of splice variants in resistance to cancer therapy
• Detection of drug resistance  
• Anaplastic lymphoma kinase..
• CRISPR for studying mechanism of drug-resistance in cancer 
• Metabolic profiling of cancer
• Management of drug resistance in cancer 
• Chemogenomic approach to drug resistance 
• Determination of chemotherapy response by topoisomerase levels
• Patient-derived xenograft mouse models in drug resistant cancer
• Resistance to vaccines in cancer recurrence after surgery
• Systems biology approach to drug-resistant cancer
• Personalized therapy of cancer metastases 
• Technologies for analysis of CTCs 
• Microfluidic technologies  
• BEAMing technology for analysis of circulating tumor DNA.
• Technologies for detection of interplay of environments and CTCs
• Systemic antitumor effect of localized radiotherapy for cancer metastases  
• Diagnosis of cancer of an unknown primary..
• Personalized management of cancers of various organs/systems
• Personalized management of bladder cancer 
• Biomarkers of bladder cancer 
• Selection of optimal anticancer agents for bladder cancer
• Personalized management of brain tumors  
• Aptamers for selective targeting of tumor initiating cells in GBM 
• Bioinformatic approach to personalizing treatment of GBM 
• Biosimulation approach to personalizing treatment of brain cancer
• Brain cancer chip for personalized drug screening 
• Combination of gene therapy and CAR-T cell therapy for GBM  
• Drug resistance in GBM.
• Genetics and genomics of GBM
• Genomic analysis as a guide to personalized therapy of GBM
• Induced neural stem cells for personalized therapy of GBM  
• Molecular diagnostics for personalized management of GBM
• Personalized vaccine for GBM 
• Personalized chemotherapy of GBM 
• Sex differences in GBM for guiding management
• Personalized therapy of oligodendroglial tumors  
• Personalized therapy of neuroblastomas
• Personalized therapy of medulloblastomas
• Personalized management of germ cell brain tumors 
• Personalized management of meningiomas
• Supratentorial hemispheric diffuse low-grade gliomas  
• Targeted therapy of BRAF V600E mutant papillary craniopharyngioma
• Future prospects of personalized therapy of malignant brain tumors  
• Personalized management of breast cancer
• Biomarker-guided decisions for breast cancer therapy
• Developing personalized drugs for breast cancer
• Gene expression plus conventional predictors of breast cancer
• Her2 testing in breast cancer as a guide to treatment  
• HER2/neu-derived peptide vaccine for breast cancer 
• Prediction of cell signaling pathways from gene expression patterns  
• Trends in treatment patterns and outcomes for DCIS  
• Molecular diagnostics in breast cancer 
• Molecular classification of infiltrating breast cancer 
• Monitoring of circulating tumor cells in breast cancer 
• Gene therapy of breast cancer  
• Pharmacogenetics of breast cancer 
• Proteomics-based personalized management of breast cancer  
• Predicting response to chemotherapy in breast cancer
• Adjuvant endocrine therapy in premenopausal breast cancer
• Prediction of resistance to chemotherapy in breast cancer
• Prediction of adverse reaction to radiotherapy in breast cancer
• Prediction of recurrence in breast cancer for personalizing therapy
• Prognostic tests for breast cancer
• Racial factors in the management of breast cancer  
• RATHER consortium to study personalized approach to breast cancer
• Ribociclib as first-line therapy for HR-positive breast cancer
• TAILORx (Trial Assigning Individualized Options for Treatment)
• Tamoxin therapy for ER-positive breast cancer 
• Triple negative breast cancer
• Treatment resistance in hormone receptor-positive breast cancer
• Current trends and future of breast cancer research
• Understanding tumor diversity in mouse mammary cancer model
• Personalized management of ovarian cancer 
• Early diagnosis of ovarian cancer  
• Determining response to chemotherapy in ovarian cancer
• Personalized PARP therapy of ovarian cancer  
• Prognosis of ovarian cancer based on CLOVAR
• Recurrent and drug-resistant ovarian cancer  
• Pathway targeted therapies for ovarian cancer 
• Repurposing auranofin for treatment of ovarian cancer
• Subtype-specific therapies for epithelial ovarian cancer 
• Targeting hematogenous metastasis of ovarian cancer
• Vynfinit ® for platinum-resistant ovarian cancer
• Personalized management of head and neck cancer
• Molecular characterization of head and neck cancer using omics 
• Relevance of biomarkers of HPV-related head and neck cancer
• Molecular targeted therapies for HNSCC..
• Personalized management of hematological malignancies
• B cell malignancies  
• Personalized management of acute lymphoblastic leukemia
• Personalized management of chronic lymphocytic leukemia  
• Personalized management of acute myeloid leukemia  
• Personalized management of chronic myeloid leukemia 
• Personalized management of multiple myeloma  
• Personalized management of myelodysplastic syndrome  
• Personalized management B cell lymphomas  
• Personalized vaccine for follicular lymphoma  
• Pharmacoproteomics approach to diffuse large B cell lymphoma 
• Companion diagnostic for treatment of lymphoma with Adcentris™ 
• Management of drug resistance in leukemia 
• Personalized management of gastrointestinal tumors 
• Personalized management of esophageal cancer
• Personalized management of gastric cancer 
• Personalized management of gastroesophageal cancer
• Personalized management of gastrointestinal stromal tumors 
• Personalized management of colorectal cancer
• Developing personalized therapies for CRC
• Molecular diagnosis for guiding personalized management of CRC
• Role of staging of CRC in prognosis and management decisions
• Role of biomarkers in personalized management of CRC  
• Role of miRNA modeling in personalized management of CRC 
• Resistance to targeted EGFR blockade in CRC
• Sequencing for personalized management of colorectal cancer
• Systems biology approach to drug resistance in colorectal cancer
• Personalized management of liver cancer
• Prognosis of HCC in relation to management  
• Prediction of recurrence of hepatocellular carcinoma 
• Prediction of survival of patients with fibrolamellar HCC 
• Personalized management of lung cancer
• ALK inhibitors for personalized management of NSCLC
• Bronchial genomic classifier for diagnostic of lung cancer
• Companion diagnosis for NSCLC therapeutics
• Copy number variations as a diagnostic tool for lung cancer
• Development of resistance to EGFR inhibitors
• EGFR mutations for predicting response to drugs in lung cancer 
• Molecular subtyping of lung cancer
• miRNA classifiers as diagnostic/prognostic tools in lung cancer
• Predicting response of NSCLC to drug therapy
• Predicting recurrence of lung cancer for prevention
• Proteomics for discovery of metabolic biomarkers of lung cancer  
• Role of a new classification system in the management of lung cancer 
• Selecting therapy of cancer arising from respiratory papillomatosis 
• Sequencing the genomes of SCLC
• Testing for response to chemotherapy in lung cancer  
• Testing for prognosis of lung cancer  
• Testing for recurrence of lung cancer
• Personalized management of malignant melanoma  
• Inhibitors of BRAF mutation for metastatic melanoma
• Management of drug-resistant metastatic melanoma 
• Vaccine for malignant melanoma based on heat shock protein  
• Personalized management of endocrine tumors 
• Adosterone producing tumors 
• Neuroendocrine tumors 
• Parathyroid tumors
• Personalized management of pheochromocytoma and paraganglioma 
• Personalized management of osteosarcoma
• Personalized management of pancreatic cancer 
• Biomarkers of pancreatic cancer 
• Histone modifications predict treatment response in pancreatic cancer  
• Transport properties of pancreatic cancer and gemcitabine delivery  
• Personlized management of prostate cancer
• Assessing susceptibility to prostate cancer by genotyping
• Diagnostics for guiding therapy of prostate cancer  
• Detection of prostate cancer metastases
• Early detection of cancer recurrence and guiding treatment
• Effects of lifestyle changes shown by gene expression studies 
• Epigenetics-based assays for guiding the decision to biopsy prostate  
• Genomic patterns of aggressiveness of prostate cancer 
• Personalized peptide vaccine for prostate cancer
• Selection of prostate cancer patients responsive to rucaparib therapy 
• Personalized management of thyroid cancer
• Current trends and future of personalized oncology  
• Challenges for developing personalized cancer therapies 
• Personalizing anticancer drug combinations
• Cancer Genome Atlas 
• Cancer Moonshot
• Blood Profiling Atlas
• NCI collaborations 
• COLTHERES consortium
• 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  
• Catalog of cancer genes for personalized therapy
• NCI-designated Comprehensive Cancer Centers  
• Role of NCI Genomic Data Commons in personalized cancer therapy
• Precision Oncology Decision Support at MD Anderson Cancer Center  
• PREDICT Consortium
• Quebec Clinical Research Organization in Cancer
• The San Antonio 1000 Cancer Genomes Project 
• Companies involved in developing personalized oncology

Tables 
Table 1-1: Selected terms relevant to the concept of personalized medicine
Table 1-2: Landmarks in the historical development of personalized medicine
Table 1-3: Genetic variations in the human genome
Table 1-4: Examples of systems medicine-based diagnostic/therapeutic approaches
Table 2-1: Molecular diagnostic technologies used for personalized medicine  
Table 2-2: Applications of biochip technology relevant to personalized medicine  
Table 2-3: Companies developing haplotying technology  
Table 2-4: Technologies for SNP analysis
Table 2-5: A sampling of companies involved in technologies for SNP genotyping  
Table 2-6: Comparison of proteomic and genomic approaches in personalized medicine
Table 2-7: Selected methods for gene expression profiling  
Table 2-8: A selection of companies with gene expression technologies
Table 2-9: Drugs requiring biomarker/companion diagnostic information in the label
Table 2-10: Companies involved in companion diagnostics  
Table 2-11: Applications of point-of-care diagnosis
Table 2-12: Companies developing point-of-care diagnostic tests
Table 2-13: Companies offering genetic screening tests directly to consumers  
Table 3-1: Pharmacogenetic vs. pharmacogenomic studies
Table 3-2: Enzymes relevant to drug metabolism  
Table 3-3: Examples of mutation of the enzyme CYP450
Table 3-4: Frequency distribution of drugs metabolized by major isoforms of CYP450. 
Table 3-5: Commonly prescribed medications, which are metabolized by CYP2D6  
Table 3-6: Polymorphisms in drug target genes that can influence drug response  
Table 3-7: Effect of genetic polymorphisms on disease response to drugs
Table 3-8: Examples of genetically determined adverse reactions to drugs 
Table 3-9: Examples of genotyping and phenotyping in some diseases
Table 3-10: Companies with novel molecular toxicology technology
Table 3-11: Pharmacogenomic biomarkers in drug labeling
Table 4-1: Role of pharmacogenomics in variable therapy targets
Table 4-2: Role of pharmacogenomics in clinical trials
Table 4-3: Examples of pharmacogenomics-based clinical studies
Table 4-4: Tumor suppressor genes, their chromosomal location, function and associated tumors.  
Table 4-5: Gene polymorphisms relevant to cardiovascular disease management  
Table 4-6: Companies involved in cardiovascular genomics
Table 4-7: SNPs in genes implicated in response of bipolar disorder to lithium
Table 4-8: A sampling of companies involved in neuropharmacogenomics
Table 5-1: Applications of pharmacoproteomic biomarkers in personalized medicine  
Table 8-1: Companies involved in personalized nutrition
Table 9-1: Important therapeutic areas for personalized medicine 
Table 9-2: Enzymes that metabolize antipsychotics
Table 9-3: Enzymes that metabolize antidepressants
Table 9-4: Biomarkers of response to antidepressant treatment  
Table 9-5: Brain imaging for diagnosis of neurodegenerative parkinsonism 
Table 9-6: Biomarkers of epilepsy
Table 9-7: Influence of gene polymorphisms on efficacy of antiepileptic drugs 
Table 9-8: Biomarkers of stroke  
Table 9-9: Role of cell therapy in management of stroke according to stage  
Table 9-10: Gene expression as biomarker of response to IFN-β in multiple sclerosis
Table 9-11: Biomarkers of traumatic brain injury 
Table 9-12: P450 isoforms in the metabolism of drugs used in the management of pain
Table 9-13: Personalized management of neuropathic pain based on mechanism  
Table 9-14: Genes that cause cardiovascular diseases
Table 9-15: Classification of diabetes into 5 clusters  
Table 9-16: Genetic influences on pharmacotherapy of alcoholism 
Table 10-1: Factors that drive the development of personalized therapy in cancer
Table 10-2: Impact of molecular diagnostics on the management of cancer  
Table 10-3: FDA-approved companion diagnostics for cancer  
Table 10-4: Marketed anticancer personalized medicines
Table 10-5: Monoclonal antibodies for cancer approved by the FDA
Table 10-6: Clinical trials of personalized cancer vaccines 
Table 10-7: Future developments in oncology relevant to personalized management
Table 10-8: Selected companies involved in developing personalized oncology  

Figures 
Figure 1-1: Relation of personalized medicine to other technologies 
Figure 1-2: Relation of systems pharmacology to personalized medicine
Figure 2-1: Role of sequencing in personalized medicine 
Figure 2-2: Role of biochip/microarray technology in personalized medicine  
Figure 2-3: Application of biochips/microarrays in personalized therapy  
Figure 2-4: Affymetrix GeneChip technology 
Figure 2-5: Role of CYP450 genotyping in development of personalized medicine
Figure 2-6: Role of SNPs in personalized medicine 
Figure 2-7: A scheme of integrated healthcare and personalized medicine
Figure 3-1: Pharmacogenetics as a link between genotype and phenotype
Figure 3-2: Role of pharmacogenetic technologies in personalized medicine  
Figure 4-1: Impact of new technologies at various stages of the drug discovery process
Figure 4-2: Steps in the application of pharmacogenomics in clinical trials
Figure 7-1: Role RNAi in development of personalized medicine 
Figure 8-1: A scheme of various factors in personalized nutrition
Figure 9-1: Pathogen sequencing as guide to personalized management viral infections
Figure 9-2: An integrated approach to viral diseases  
Figure 9-3: Workflow of genotypic resistance analysis for personalized HIV therapy 
Figure 9-4: Gene-environment interactions leading to an increased risk of cardiac death in COVID-19
Figure 9-5: Components of multimodal therapy for neurological disorders
Figure 9-6: Scheme of iPSCs use for personalized cell therapy of Parkinson disease 
Figure 9-7: Antisense approaches for personalized therapy of Huntington disease
Figure 9-8: An algorithm for personalized management of epilepsy  
Figure 9-9: Interacting risk factors for stroke
Figure 9-10: Decision for medical vs surgical treatment of carotid occlusive disease 
Figure 9-11: Algorithm for anticoagulant therapy to prevent stroke in atrial fibrillation 
Figure 9-12: Spot sign of extravasation and expansion of intracerebral hematoma
Figure 9-13: A scheme of personalized therapy of multiple sclerosis
Figure 9-14: Personalized targeting of therapeutic agents to lesions of multiple sclerosis
Figure 9-15: Essential components of personalized management of pain  
Figure 9-16: Genetic and non-genetic factors affecting efficacy and side effects of opioids  
Figure 9-17: Role of opioid therapy in management of noncancer pain
Figure 9-18: An algorithm for personalized management of pain
Figure 9-19: Assessment of stable coronary artery disease
Figure 9-20: Flow chart of personalized approach to management of atrial fibrillation
Figure 9-21: A scheme of personalized approach to management of chronic hypertension  
Figure 9-22: Statins for management of blood cholesterol to reduce risk of CVD
Figure 9-23: Basis of personalized approach to idiopathic pulmonary fibrosis (IPF)
Figure 9-24: Steps in growing a new heart in vitro for transplantation  
Figure 10-1: Relationships of technologies for personalized management of cancer
Figure 10-2: Integration of technologies for personalized prevention of cancer 
Figure 10-3: CRISPR-Cas9 in personalized cancer gene therapy  
Figure 10-4: Use of LC-MS/MS to select appropriate targeted therapy for cancer 
Figure 10-5: Personalized cancer therapy based on targeted proteomics
Figure 10-6: Applications of NCI Genomic Data Commons  
Figure 10-7: Workflow for development of gene pages for personalized cancer therapy  

Part II: Development, Ethics, Regulation, Markets & Companies

11. Development of Personalized Medicine 

• Introduction  
• Non-genomic factors in the development of personalized medicine  
• Personalized medicine based on circadian rhythms 
• Cytomics as a basis for personalized medicine 
• Intestinal microflora 
• Gut microbiome compared to human genome 
• Metabolic interactions of the host and the intestinal microflora 
• Role of drug delivery in personalized medicine 
• 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 
• Players in the development of personalized medicine  
• Personalized Medicine Coalition
• Role of pharmaceutical industry 
• Repositioning of drugs for personalized medicine  
• Discovery of personalized medicines
• Personalized drug delivery
• Production and distribution of personalized medicines
• Role of biotechnology companies
• Role of life sciences industries
• Role of biomedical engineering in wearable devices for personalized healthcare
• Role of molecular imaging in personalized medicine 
• Molecular imaging for personalized drug development in oncology  
• Molecular imaging and CNS drug development
• Companies involved in molecular imaging
• 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
• NIH's Roadmap Initiative for Medical Research
• NIH and personalized medicine 
• NIH collaboration with the FDA 
• NIH and Genetic Testing Registry
• National Human Genome Research Institute
• National Institute of General Medical Sciences  
• National Institute of Standards and Technology
• Role of the Centers for Disease Control
• Role of academic institutions and health centers in the US  
• Baylor College of Medicine 
• California Initiative to Advance Precision Medicine
• Children’s Hospital of Los Angeles 
• Clinical Proteomics Program of NCI & FDA
• Coriell Personalized Medicine Collaborative™
• Delaware Valley Personalized Medicine Project  
• Duke University’ Center for Genomic and Computational Biology
• Evaluation of genetic tests and genomic applications
• Indiana University Institute for Personalized Medicine
• Inova Center for Personalized Health 
• Institute of Medicine’s role in personalized medicine  
• Jackson Laboratory for Genomic Medicine
• Johns Hopkins Center for Personalized Cancer Medicine Research 
• Mayo Clinic’s Centers for Individualized Medicine  
• Mt. Sinai Medical Center’s Personalized Medicine Research Program
• North Shore University’s Center for Personalized Medicine  
• P4 Medicine Institute
• Personalized Medicine Partnership of Florida
• Personalized oncology at Massachusetts General Hospital  
• Personalized oncology at Oregon Health & Science University
• Pharmacogenetics Research Network and Knowledge Base
• Southeast Nebraska Cancer Center's Personalized Medicine Network 
• Spectrum Health Center for personalized cancer care
• Stanford Center for Genomics and Personalized Medicine 
• UAB-HudsonAlpha Center for Genomic Medicine
• University of Colorado’s Center for Personalized Medicine 
• UNC Institute for Pharmacogenomics and Individualized Therapy
• Weill Cornell’s Englander Institute for Precision Medicine
• Wisconsin Genomics Initiative.
• Role of academic collaborations with companies
• New York Genome Center  
• Role of healthcare organizations  
• Role of the medical profession
• The American Medical Association and personalized medicine
• Education of the physicians
• Off-label prescribing and personalized medicine
• Medical education
• Role of patients
• Consumer genomics  
• Monitoring of patient compliance with therapy  
• Public attitude towards personalized medicine  
• Patient participation in disease management decisions  
• Patient engagement in clinical trials of 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 
• BBMRI-ERIC
• 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 
• Devices for detection of digital biomarkers 
• Clinical decision support systems
• Digitalized medicine 
• Genomic data analysis
• Integration of omics data by deep learning
• Exploration of disease-gene relationship 
• Health information management  
• Electronic health records
• Analysis of -omic and EHR data of the patient
• Cost of EHR and savings on healthcare expenses in the US
• EHRs and genome-wide studies  
• Linking patient medical records and genetic information
• Management of personal genomic data
• Use of EHRs for improving safety of new medicines 
• Use of EHRs for genetic research
• Use of EHRs for personalized drug discovery and development 
• Personalized prognosis of disease
• Integration of technologies for personalized medicine
• 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
• 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 
• Advantages of personalized medicine  
• Limitations of personalized medicine 
• Non-genomic factors in response to drugs
• Incidental findings in genetic screening and clinical sequencing 
• Future of personalized medicine  
• Personal Genome Project
• Genome-wide association studies
• NHGRI’s genomics vision for 2020 
• Genomics of aging in a genetically homogeneous population  
• Translational science and personalized medicine
• Translation of genomic research into genetic testing for healthcare
• Long-term behavioral effects of personal genetic testing
• Personalized predictive medicine  
• Connected health and personalized medicine
• Opportunities and challenges for personalized medicine  
• Comparative-effectiveness research and personalized medicine  
• Genetic testing and concerns about equality of healthcare 
• Impact of molecular diagnostics on personalized medicine
• Initiative for delivery for precision medicine
• IGNITE network - implementing personalized medicine in clinical care
• Prospects and limitations of genetic testing  
• Personalized medicine and public health  
• Pharmacotyping
• Medicine in the year 2025  
• Concluding remarks about the future of personalized medicine

12. Ethical, Legal and Regulatory Aspects of 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 the US
• UNESCO and ethical aspects of personalized medicine 
• Genotype-specific clinical trials
• Ethical issues in the use of digital technologies for personalized medicine 
• Social issues in personalized medicine  
• Race and personalized medicine 
• Legal issues of personalized medicine
• Gene patents and personalized medicine
• Regulatory aspects  
• FDA and personalized medicine 
• FDA and molecular diagnostics in relation to personalized medicine
• CLSI guideline for the use of RNA controls in gene expression assays
• Evaluation of companion diagnostics/therapeutic
• FDA oversight of laboratory developed tests 
• FDA guidelines for the role of IVD in personalized medicine  
• FDA oversight of NGS for diagnosis in personalized medicine
• FDA’s Clinical Databases Guidance
• Analytical Validation Guidance  
• IVD device and drug co-development
• FDA guidelines for personalized oncology 
• Regulatory aspects of pharmacogenetics
• Regulation of direct-to-consumer genetic testing
• Need for regulatory oversight of DTC
• FDA and pharmacogenomics
• FDA guidance for pharmacogenomic data submissions
• Joint guidelines of the FDA and EU regulators for pharmacogenomics
• Pharmacogenomic (PGx) information in drug labels
• FDA guidelines for pharmacogenomics-based dosing 
• FDA and validation of biomarkers  
• FDA and predictive medicine

13. Markets for Personalized Medicine  

• Introduction  
• 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 
• Reducing healthcare costs by combining diagnostics with therapeutics 
• 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 
• Cost-benefit analysis of KRAS and BRAF screening in CRC
• Lowering the high costs of cancer chemotherapy
• Personalized dose reduction of pembrolizumab in cancer
• Overall impact of personalized medicine on healthcare
• Drivers for the development of personalized medicine  
• Evolution of medicine as a driver for personalized therapy markets
• Collaboration between the industry and the academia  
• Personalized medicine and drug markets  
• Segmentation of therapeutic drug markets  
• Reasons for increase of market values of personalized medicines 
• Growth of markets relevant to personalized medicine 
• Biochips for diagnosis  
• Pharmacogenetics 
• Pharmacogenomics
• Pharmacoproteomics 
• Point-of-Care  
• SNP market
• Markets for personalized medicines according to therapeutic areas
• Market for personalized cancer therapy  
• Markets for immuno-oncology  
• Markets for personalized medicines according to geographical regions
• Market opportunities for personalization of medicine
• Impact of personalized medicine on other industries.
• Strategies for developing and marketing personalized medicine
• Education of the public
• Role of the Internet in the development of personalized medicine 
• Marketing companion diagnostics for personalized medicine

14. Companies Involved in Developing Personalized Medicine  

• Introduction  
• Profiles  
• Collaborations

15. References

Tables 
Table 11-1: Bayesian versus frequentist approaches in clinical trials  
Table 11-2: Players in the development of personalized medicine  
Table 11-3: Members of the Personalized Medicine Coalition
Table 11-4: Biobanks relevant to personalized medicine 
Table 11-5: Role of bioinformatics in the development of personalized medicine  
Table 11-6: Advantages of personalized medicine for the biopharmaceutical industry 
Table 11-7: Advantages of personalized medicine for the patients
Table 11-8: Advantage of personalized medicine for the physicians
Table 11-9: Advantage of personalized medicine for the healthcare providers
Table 11-10: Limitations of personalized medicine 
Table 11-11: Recommendations of the Association for Molecular Pathology on incidental findings  
Table 11-12: Methods of translational science that are relevant to personalized medicine 
Table 11-13: Companies involved in predictive healthcare
Table 11-14: Delivery for precision medicine 
Table 12-1: Drugs with pharmacogenomic information in their labels 
Table 13-1: Drivers for the development of personalized medicine 
Table 13-2: Growth of markets relevant to personalized medicine 2020-2030 
Table 13-3: Markets for personalized medicine according to therapeutic area 2020-2030
Table 13-4: Markets for personalized medicine in major regions 2020-2030  
Table 13-5: Lack of efficacy in current therapy  
Table 13-6: Impact of personalized medicine on other industries
Table 13-7: Strategies to develop personalized medicine
Table 13-8: Role of the Internet in the development of personalized medicine
Table 14-1: Top five pharmaceutical companies involved in personalized medicine
Table 14-2: Selected collaborations of companies in personalized medicine 

Figures
Figure 13-1: Cost of sequencing per genome
Figure 13-2: Evolution of personalized medicine as a market driver