個別化醫療：科學的・商業的情勢 是由出版商Jain Pharmabiotech在2012年01月所出版的。
這份英文市場調查報告書價格從美金5000起跳。
個別化醫療的目的在於給患者適當的醫療藥品的處方簽及有時可針對患者的基因型態設計適合的治療方法。
本報告書內容包括：依據藥理基因體學、藥理遺傳學、藥理蛋白質體學及代謝學調查個別化醫療的最新概念、內容綱要摘記如下：
第1部分
- 實施概要
- 基本情勢
- 個別化醫療的分子診斷
- 藥理遺傳學
- 藥理基因體學
- 藥理蛋白質體學的作用
- 個別化醫療在代謝體學上的作用
- 個別化生物療法
- 主要治療區分的個別化醫療
- 癌症的個別化醫療
- 個別化醫療的開發
- 個別化醫療的倫理・限制狀況
- 個別化醫療的商業情勢
- 參考
第2部分
Abstract
Summary
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 2014.
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 2010-2020.
Profiles of 244 companies involved in developing technologies for personalized
medicines, along with 458 collaborations are included in the part II of the
report. Finally the bibliography contains over 600 selected publications cited
in the report.The report is supplemented by 63 tables and 17 figures.
Table of Contents
0. Executive Summary
1. Basic Aspects
- Definition of personalized medicine
- History of medical concepts relevant to personalized medicine
- Molecular biological basis of personalized medicine
- The human genome
- 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
- Basics technologies for developing personalized medicine
- Definitions of technologies relevant to personalized medicine
- Problems with the ICH definitions of pharmacogenomcis and pharmacogenetics
- Relationship of various technologies to personalized medicine
- Conventional medicine versus personalized 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
- Genetic epidemiology
- Limitations of medical genetics and future prospects
- Genetics vs. epigenetics
- Role of systems biology in personalized medicine
- Systems pharmacology
- Systems medicine
- Synthetic biology and development of personalized medicines
- A personalized approach to environmental factors in disease
- Reclassification of diseases
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 PRISMR 310 Genetic Analyzer
- High-throughput paired end transcriptome sequencing
- Emerging sequencing technologies
- 4300 DNA analyzer
- Apollo 100
- Color blind approach to DNA sequencing
- Cyclic array sequencing
- CEQ"! 8000
- DeepCAGE sequencing
- Electron microscope-based DNA sequencing
- Genometrica™ sequencer
- GS-FLEX system (Roche/454)
- IBS sequencing technology
- Illumina Genome Analyzer System
- MegaBACE 500
- Microdroplet-based PCR for large-scale targeted sequencing
- Multiplex amplification of human DNA sequences
- Nanoscale sequencing
- Polonator sequencer
- RainStorm"! microdroplet technology
- Sequential DEXAS
- SOLiD technology
- Sequencing by hybridization
- Whole genome sequencing
- Bioinformatic tools for analysis of genomic sequencing data
- 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 sequencing in development of personalized medicine
- Biochips and microarrays
- Application of biochip technology in developing 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
- Biochip combining BeadArray and ZipCode technologies
- SNP-IT primer-extension technology
- Affymetrix Variation Detection Arrays
- Use of NanoChip for detection of SNPs
- Electrochemical DNA probes
- Single base extension-tag array
- Laboratory Multiple Analyte Profile
- PCR-CTPP (confronting two-pair primers)
- SNP genotyping on a genome-wide amplified DOP-PCR template
- TaqMan real-time PCR
- Non-Enzymatic Amplification Technology
- SNP genotyping with gold nanoparticle probes
- Locked nucleic acid
- Molecular inversion probe based assays
- Pyrosequencing
- Reversed enzyme activity DNA interrogation test
- Smart amplification process version 2
- Zinc finger proteins
- UCAN method (Takara Biomedical)
- 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
- Study of rare variants in pinpointing disease-causing genes
- Optical Mapping
- Role of nanobiotechnology in molecular diagnostics
- Cantilevers for personalized medical diagnostics
- Nanopore-based technology for single molecule identification
- Role of biomarkers in personalized medicine
- Biomarkers for diagnostics
- Biomarkers for drug development
- Application of 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
- Gene expression profiling
- DNA microarrays
- Analysis of single-cell gene expression
- Gene expression profiling based on alternative RNA splicing
- Whole genome expression array
- Tangerine"! expression profiling
- Gene expression analysis on biopsy samples
- Profiling gene expression patterns of white blood cells
- Serial analysis of gene expression (SAGE)
- Multiplexed Molecular Profiling
- Gene expression analysis using competitive PCR and MALDI TOF MS
- Monitoring in vivo gene expression by magnetic resonance imaging
- Companies involved in gene expression analysis
- Monitoring in vivo gene expression by molecular imaging
- Molecular imaging and personalized medicine
- Glycomics-based diagnostics
- 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
- 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
- P450 CYP 2D6 inhibition by selective serotonin reuptake inhibitors
- 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 antiplatelet therapy with clopidrogrel
- 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
- 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
- Pharmacogenomic biomarker information in drug labels
- Genotype-based drug dose adjustment
- Examples of use of pharmacogenetics in clinical pharmacology
- 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
- 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 schizophrenia
- Companies involved in neurogenomics-based drug discovery
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
- Role of reverse-phase protein microarray in drug discovery
- Role of proteomics in clinical drug safety
- Toxicoproteomics
- Application 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
- Validation of biomarkers in large-scale human metabolomics studies
- Pharmacometabonomics
- Metabonomic technologies for toxicology studies
- Metabonomics/metabolomics and personalized nutrition
7. Personalized Biological Therapies
- Introduction
- Recombinant human proteins
- Therapeutic monoclonal antibodies
- Cell therapy
- Autologous tissue and cell transplants
- Stem cells
- Role of stem cells derived from unfertilized embryos
- Cloning and personalized cell therapy
- Use of stem cells for drug testing
- Gene therapy
- Personalized vaccines
- Personalized vaccines for viral diseases
- Personalized cancer vaccines
- Antisense therapy
- RNA interference
- MicroRNAs
8. Personalized Medicine in Major Therapeutic Areas
- Introduction
- Management of infections
- 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 HIV
- Role of genetic variations in susceptibility to HIV-1
- Personalized treatment of hepatitis B
- Personalized treatment of hepatitis C
- Personalized management of tuberculosis
- Psychiatric disorders
- Psychopharmacogenetics
- COMT genotype and response to amphetamine
- Genotype and response to methylphenidate in children with ADHD
- Personalized antipsychotic therapy
- Personalized antidepressant therapy
- EEG to predict adverse effects and evaluate antidepressant efficacy
- Individualization of SSRI treatment
- Vilazodone with a test for personalized treatment of depression
- Neurological disorders
- Personalized management of Alzheimer's disease
- Personalized management of Parkinson's disease
- Discovery of subgroup-selective drug targets in PD
- Personalized management of Epilepsy
- Choice of the right AED
- Pharmacogenetics of epilepsy
- Pharmacogenomics of epilepsy
- Drug resistance in epilepsy
- Future prospects for management of epilepsy
- Personalized management of migraine
- Individualization of use of triptans for migraine
- Personalized management of stroke
- Brain imaging in trials of restorative therapies for stroke
- Decisions for evacuation of intracerebral hemorrhage
- Revascularization procedures in chronic post-stroke stage
- Personalized treatment of multiple sclerosis
- Immunopathological patterns of demyelination for assessing therapy
- Personalizing mitoxantrone therapy of multiple sclerosis
- Fusokine method of personalized cell therapy of multiple sclerosis
- MBP8298
- Pharmacogenomics of IFN-β therapy in multiple sclerosis
- T cell-based personalized vaccine for MS
- Cardiovascular disorders
- Role of diagnostics in personalized management of cardiovascular disease
- Testing in coronary heart disease
- SNP genotyping in cardiovascular disorders
- Cardiovascular disorders with a genetic component
- Gene variant as a risk factor for sudden cardiac death
- KIF6 gene test as a guide to management of heart disease
- SNP Chip for study of cardiovascular diseases
- Pharmacogenomics of cardiovascular disorders
- Modifying the genetic risk for myocardial infarction
- Management of heart failure
- β-blockers
- Bucindolol
- BiDil
- Management of hypertension
- Pharmacogenomics of diuretic drugs
- Pharmacogenomics of ACE inhibitors
- Management of hypertension by personalized approach
- Prediction of antihypertensive activity of rostafuroxin
- Pharmacogenetics of lipid-lowering therapies
- Polymorphisms in genes involved in cholesterol metabolism
- Role of eNOS gene polymorphisms
- The STRENGTH study
- Personalized management of women with hyperlipidemia
- Thrombotic disorders
- Factor V Leiden mutation
- Anticoagulant therapy
- Antiplatelet therapy
- Nanotechnology-based personalized therapy of cardiovascular diseases
- Project euHeart for personalized management of heart disease
- Concluding remarks
- Personalized management of pulmonary disorders
- Role of genetic ancestory in lung function
- Personalized therapy of asthma
- 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
- Personalized management of skin disorders
- Genetic testing for personalized skin care
- Management of hair loss based on genetic testing
- Personalized therapy of rheumatoid arthritis
- DIATSTAT"! anti-cyclic citrullinated peptides in rheumatoid arthritis
- Personalization of COX-2 inhibitor therapy
- Personalization of infliximab therapy
- Personalized approaches in immunology
- Role of Mannose-binding lectin in personalized medicine
- Pharmacogenetics and pharmacogenomics of immunosuppressive agents
- Personalized management of patients with lupus erythematosus
- Personalized management of pain
- Pharmacogenetics/pharmacogenomics of pain
- Mechanism-specific management of pain
- Preoperative testing to tailor postoperative analgesic requirements
- Personalized analgesics
- Management of genetic disorders
- Personalized treatment of cystic fibrosis
- 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
- Personalization of cardiac transplantation
- Prediction of rejection to tailor anti-rejection medications
- Personalized immunosuppressant therapy in organ transplants
- Role of immunological biomarkers in monitoring grafted patients
- Improved matching of blood transfusion
- Personalized approach to addiction
- Pharmacogenetics of drug addiction
- Genetic polymorphism and management of alcoholism
- Personalized therapy for smoking cessation
- Antidepressant therapy for smoking cessation
- Effectiveness of nicotine patches in relation to genotype
- Personalized approaches to miscellaneous problems
- Hormone replacement therapy in women
- Personalized treatment of malaria
- Personalized management of renal disease
- Gene associated with end-stage renal disease
- Personalized care of trauma patients
- Personalized anticoagulation
- Personalized Hyperbaric oxygen therapy
- Personalized preventive medicine
- Personalized nutrition
- Nutrigenomics
- Genomics of vitamin D and calcium supplementation
- Nutrigenomics and functional foods
- Nutrigenetics and personalized medicine
- Nutrigenomics and personalized medicine
- Nutrition and proteomics
- Personalized diet prescription
9. Personalized Therapy of Cancer
- Introduction
- Challenges of cancer classification
- Relationships of technologies for personalized management of cancer
- Impact of molecular diagnostics on the management of cancer
- AmpliChip P53 as companion diagnostic for cancer
- Analysis of RNA splicing events in cancer
- Analysis of chromosomal alterations in cancer cells
- Cancer classification using microarrays
- Detection of loss of heterozygosity
- Diagnosis of cancer of an unknown primary
- Diagnostics for detection of minimal residual disease
- DNA repair biomarkers
- Fluorescent in situ hybridization
- Gene expression profiling
- Gene expression profiles predict chromosomal instability in tumors
- Isolation and characterization of circulating tumor cells
- Modulation of CYP450 activity for cancer therapy
- 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
- Tumor imaging and elimination by targeted gallium corrole
- Future prospects of molecular imaging in management of cancer
- Unraveling the genetic code of cancer
- Cancer prognosis
- Detection of mutations for risk assessment and prevention
- Impact of biomarkers on management of cancer
- HER-2/neu oncogene as a biomarker for cancer
- L-asparaginase treatment of cancer guided by a biomarker
- Oncogene GOLPH3 as a cancer biomarker
- Predictive biomarkers for cancer
- Sequencing to discover biomarkers to personalize cancer treatment
- Systems biology approach to discovery of radiation sensitivity biomarkers
- VeraTag"! assay system for cancer biomarkers
- Determination of response to therapy
- ChemoFx cell culture assay for predicting anticancer drug response
- 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
- Genomic analysis of tumor biopsies
- Genotype-dependent efficacy of pathway inhibition in cancer
- Mutation detection at molecular level
- Role of genetic variations in susceptibility to anticancer drugs
- Non-genetic factors for variations in response of cancer cells to drugs
- 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
- Tissue systems biology approach to personalized management of cancer
- Targeted cancer therapies
- Targeting glycoproteins on cell surface
- Targeting pathways in cancer
- Functional antibody-based therapies
- Personalized cancer vaccines
- Antigen-specific vaccines
- Active immunotherapy based on antigen specific to the tumor
- Tumor-derived vaccines
- 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
- Current status and future prospects of personalized cancer vaccines
- Personalized radiation therapy
- Molecular diagnostics combined with cancer therapeutics
- Aptamers for combined diagnosis and therapeutics of cancer
- Role of nanobiotechnology in personalized management of cancer
- Design of future cancer therapies
- Screening for personalized anticancer drugs
- Role of epigenetics in development of personalized cancer therapies
- Personalized therapy of cancer based on cancer stem cells
- Role of oncoproteomics in personalized therapy of cancer
- Cancer tissue proteomics
- 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
- Role of computational models in personalized anticancer therapy
- A computational model of kinetically tailored treatment
- Mathematical modeling of tumor mivroenvironments
- Molecular profiling of cancer
- Drug resistance in cancer
- Detection of drug resistance in cancer by metabolic profiling
- Determination of chemotherapy response by topoisomerase levels
- Anaplastic lymphoma kinase
- Management of drug resistance in leukemia
- Overexpression of multidrug resistance gene
- P53 mutations
- A chemogenomic approach to drug resistance
- Systems biology approach to personalizing therapy for drug-resistant cancer
- Examples of personalized management of cancer
- Personalized management of brain cancer
- Biosimulation approach to personalizing treatment of brain cancer
- Genetics and genomics of brain cancer
- Prognosis of glioblastoma multiforme based on its genetic landscape
- Molecular diagnostics for personalized management of brain cancer
- Personalized chemotherapy of brain tumors
- Personalized therapy of oligodendroglial tumors (OTs)
- Personalized therapy of neuroblastomas
- Personalized therapy of medulloblastomas
- Personalized management of germ cell brain tumors
- Personalized management of breast cancer
- 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
- Molecular diagnostics in breast cancer
- Pharmacogenetics of breast cancer
- Proteomics-based personalized management of breast cancer
- Predicting response to chemotherapy in 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
- Prognosistic tests for breast cancer
- Racial factors in the management of breast cancer
- RATHER consortium to study personalized approach to breast cancer
- TAILORx (Trial Assigning Individualized Options for Treatment)
- Trends and future prospects 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
- Recurrent and drug-resistant ovarian cancer
- Pathway targeted therapies for ovarian cancer
- Personalized management of hematological malignancies
- Personalized management of acute lymphoblastic leukemia
- Personalized management of acute myeloid leukemia
- Personalized management of chronic lymphocytic leukemia
- Personalized management of multiple myeloma
- Personalized management B cell lymphomas
- Personalized vaccine for follicular lymphoma
- Personalized management of myelodysplastic syndrome
- Personalized management of hepatocellular carcinoma
- Personalized management of gastrointestinal cancer
- Personalized management of esophageal cancer
- Personalized management of gastric cancer
- Personalized management of colorectal cancer
- A systems biology approach to drug resistance in colorectal cancer
- Personalized management of liver cancer
- Personalized management of lung cancer
- Determination of outcome of EGFR tyrosine kinase inhibitor treatment
- Crizotinib for personalized management of NSCLC
- Testing for response to chemotherapy in lung cancer
- Testing for prognosis of lung cancer
- Testing for recurrence of lung cancer
- Role of a new classification system in the management of lung cancer
- Personalized therapy of NSCLC based on KIF5B/RET fusion oncogene
- Personalized management of malignant melanoma
- Therapy for inhibiting BRAF mutation in melanoma
- Vaccine for malignant melanoma based on heat shock protein
- Personalized management of pancreatic cancer
- Biomarkers of pancreatic cancer
- Histone modifications predict treatment response in pancreatic cancer
- Personlized management of prostate cancer
- Diagnostics for guiding therapy of prostate cancer
- Early detection of cancer recurrence and guiding treatment
- Effects of of lifestyle changes shown by gene expression studies
- Personalized peptide vaccine for prostate cancer
- Future of cancer therapy
- Challenges for developing personalized cancer therapies
- Cancer Genome Atlas
- 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
- PREDICT Consortium
- Companies involved in developing personalized cancer therapy
10. 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
- Use of Bayesian approach in clinical trials
- Individualzing risks and benefits in clinical trials
- Clinical trials of therapeutics and companion diagnostics
- Players in the development of personalized medicine
- Personalized Medicine Coalition
- European Personalized Medicine Diagnostics Association
- Role of pharmaceutical industry
- Production and distribution of personalized medicines
- Role of biotechnology companies
- Role of life sciences industries
- 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
- 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 Institute of General Medical Sciences
- National Institute of Standards and Technology
- Role of the Centers for Disease Control
- Role of academic institutions in the US and Canada
- Clinical Proteomics Program
- Coriell Personalized Medicine Collaborative"!
- Delaware Valley Personalized Medicine Project
- Evaluation of genetic tests and genomic applications
- Genomic-Based Prospective Medicine Project
- Ignite Institute
- Johns Hopkins Center for Personalized Cancer Medicine Research
- Indiana University Institute for Personalized Medicine
- Jackson Laboratory for Genomic Medicine
- Role of Institute of Medicine
- Personalized medicine at Ontario Institute for Cancer Research
- Personalized oncology at Massachusetts General Hospital
- Personalized oncology at Oregon Health & Science University
- Pharmacogenetics Research Network and Knowledge Base
- Quebec Center of Excellence in Personalized Medicine
- Southeast Nebraska Cancer Center's Personalized Medicine Network
- Stanford Center for Genomics and Personalized Medicine
- UNC Institute for Pharmacogenomics and Individualized Therapy
- Wisconsin Genomics Initiative
- Role of academic collaborations with companies
- New York Genome Center
- Role of healthcare organizations and hospitals
- Signature Genetics
- The Mayo Clinic genetic database
- Research center for personalized medicine at Mt. Sinai Medical Center
- Role of the medical profession
- The American Medical Association and personalized medicine
- Education of the physicians
- Off-label prescribing and personalized medicine
- Medical education
- Public attitude towards personalized medicine
- Role of genetic banking systems and databases
- Role of biobanks in development of personalized medicine
- UK Biobank
- Biobanking and development of personalized medicine in EU
- CARTaGENE for biobanks in Canada
- Personalized medicine based on PhysioGenomics"! technology
- Role of bioinformatics in development of personalized medicine
- Exploration of disease-gene relationship
- Biosimulation techniques for developing personalized medicine
- Health information management
- Electronic health records
- Linking patient medical records and genetic information
- Management of personal genomic data
- Use of EMRs for genetic research
- Personalized prognosis of disease
- Integration of technologies for development of personalized medicine
- Global scope of personalized medicine
- Personalized medicine in the developed countries
- Personalized medicine in the US
- Personalized medicine in the EU
- UK National Health Service and medical genetics
- Personalized medicine in Germany
- Personalized medicine in the developing countries
- Advantages and limitations of personalized medicine
- Limitations of personalized medicine
- Future of personalized medicine
- Ongoing genomic projects
- Understanding the genetic basis of diseases
- Personal Genome Project
- Genome-wide association studies
- The 1000 Genomes Project
- 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
- Opportunities and challenges
- Prospects and limitations of genetic testing
- Genetic testing and concerns about equality of healthcare
- Pharmacotyping
- Comparative-effectiveness research and personalized medicine
- Medicine in the year 2015
- Concluding remarks about the future of personalized medicine
11. Ethical 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
- Ethical aspects of direct-to-consumer genetic services
- Privacy issues in personalized medicine
- Genetic Information Nondiscrimination Act in the US
- Genotype-specific clinical trials
- Social issues in personalized medicine
- Race and personalized medicine
- Regulatory aspects
- CLSI guideline for the use of RNA controls in gene expression assays
- MicroArray Quality Control Project
- 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/pharmacogenetic information in drug labels
- FDA guidelines for pharmacogenomics-based dosing
- FDA and validation of biomarkers
- FDA and predictive medicine
- FDA regulation of multivariate index assays
- Evaluation of companion diagnostics/therapeutic
12. Commercial Aspects of 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
- 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
- Lowering the high costs of cancer chemotherapy
- 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
- Impact on drug markets
- Growth of markets relevant to personalized medicine
- SNP market
- Pharmacogenomics
- Pharmacogenetics
- Pharmacoproteomics
- Biochips
- Point-of-Care
- Markets for personalized medicines according to therapeutic areas
- 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 development of personalized medicine
- Marketing companion diagnostics for personalized medicine
13. References
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 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: Companies involved in companion diagnostics
- Table 2 10: Applications of point-of-care diagnosis
- Table 2 11: Companies developing point-of-care diagnostic tests
- Table 2 12: 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 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: A sampling of companies involved in neuropharmacogenomics
- Table 8 1: Important therapeutic areas for personalized medicine
- Table 8 2: Enzymes that metabolize antipsychotics
- Table 8 3: Enzymes that metabolize antidepressants
- Table 8 4: Biomarkers of response to interferon-β-in multiple
sclerosis
- Table 8 5: Genes that cause cardiovascular diseases
- Table 9 1: Factors that drive the development of personalized therapy in
cancer
- Table 9 2: Impact of molecular diagnostics on the management of cancer
- Table 9 3: Clinical trials of personalized cancer vaccines
- Table 9 4: Selected companies involved in developing personalized cancer
therapies
- Table 10 1: Players in the development of personalized medicine
- Table 10 2: Members of the Personalized Medicine Coalition
- Table 10 3: Biobanks relevant to personalized medicine
- Table 10 4: Role of bioinformatics in the development of personalized
medicine
- Table 10 5: Advantages of personalized medicine for the biopharmaceutical
industry
- Table 10 6: Advantages of personalized medicine for the patients
- Table 10 7: Advantage of personalized medicine for the physicians
- Table 10 8: Advantage of personalized medicine for the healthcare providers
- Table 10 9: Limitations of personalized medicine
- Table 10 10: Methods of translational science that are relvant to
personalized medicine
- Table 10 11: Companies involved in predictive healthcare
- Table 11 1: Drugs with genetic information in their labels
- Table 12 1: Drivers for the development of personalized medicine
- Table 12 2: Growth of markets relevant to personalized medicine 2011-2021
- Table 12 3: Markets for personalized medicine according to therapeutic
area 2011-2021
- Table 12 4: Markets for personalized medicine in major regions 2011-2021
- Table 12 5: Lack of efficacy in current therapy
- Table 12 6: Impact of personalized medicine on other industries
- Table 12 7: Strategies to develop personalized medicine
- Table 12 8: Role of the Internet in development of personalized medicine
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 biochips/microarrays in personalized medicine
- Figure 2 3: Affymetrix GeneChip technology
- Figure 2 4: Role of CYP450 genotyping in development of personalized
medicine
- Figure 2 5: Role of SNPs in personalized medicine
- Figure 2 6: 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 personalized approach to management of hypertension
- Figure 8 2: A scheme of personalized management of pain
- Figure 9 1: Relationships of technologies for personalized management of
cancer
- Figure 10 1: Integration of technologies for the development of
personalized medicine
- Figure 12 1: Evolution of personalized medicine as a market driver
