Biomarkers - technologies,markets and companies

Table of Contents

0. Executive Summary

1. Introduction

• Definitions
• Historical aspects of biomarkers
• Classification of biomarkers
• Biological marker as response to therapeutic intervention
• Pharmacokinetic/pharmacodynamics biomarkers
• Predictive biomarkers
• Valid biomarkers
• Types of biomarkers
• Genes as biomarkers
• Proteins as biomarkers
• Proteomics
• DNA biomarkers
• Mitochondrial DNA
• Mitochondrial mutations
• RNA biomarkers
• Transcriptomics
• MicroRNAs
• Metabolomics
• Glycomics
• Single nucleotide polymorphisms
• Haplotyping
• Cell biomarkers of disease
• Stem cell biomarkers
• Association of stem cell biomarkers with disease
• Cancer stem cell biomarkers
• Endoglin as a functional biomarker of stem cells
• p75NTR as a biomarker to isolate adipose tissue-derived stem cells
• Protein expression profile as biomarker of stem cells
• STEMPRO® ZChek™ for analysis of biomarkers of hESCs
• SSEA-4 as biomarker of MSCs
• Autoantibodies as biomarkers of autoimmune diseases
• Biomarkers and systems biology
• Systems biology approach to biomarker identification
• Relation of biomarkers to other technologies and healthcare
• Biomarkers and translational medicine
• Limitations of use of biomarkers in healthcare

2. Technologies for Discovery of Biomarkers

• Introduction
• The ideal biomarker
• Genomic technologies
• Gene expression
• Whole genome expression array
• Gene expression profiling on whole blood samples
• Profiling gene expression patterns of white blood cells
• Tissue microarrays for study of biomarkers
• Epigenomic technologies
• Discovery of methylation biomarkers
• Proteomic technologies
• 2D GE
• Isotope-coded affinity tags
• Mass spectrometry
• MALDI mass spectrometry for biomarker discovery
• 2D PAGE and mass spectrometry
• Quantitative tandem MS
• Single-molecule mass spectrometry using a nanopore
• Imaging mass spectrometry
• Requirements for MS-based proteomic biomarker development
• Liquid chromatography-MS/MS
• Biomarker Amplification Filter
• Protein tomography
• Protein biochips/microarrays and biomarkers
• Detection of biomarkers using peptide array technology
• Protein nanobiochip
• Antibody-based biomarker discovery
• Real-time PCR for quantification of protein biomarkers
• Magnetics beads for protein biomarker discovery
• CellCartaR proteomics platform
• MASStermind"!
• Search for biomarkers in body fluids
• Challenges and strategies for discovey of protein biomarkers in plasma
• 3-D structure of CD38 as a biomarker
• BD"! Free Flow Electrophoresis System
• Isotope tags for relative and absolute quantification
• Plasma protein microparticles as biomarkers
• Proteome partitioning
• Stable isotope tagging methods
• Technology to measure both the identity and size of the biomarker
• Biomarkers in the urinary proteome
• Peptides in body fluids and tissues as biomarkers of disease
• Analysis of peptides in bodily fluids
• Serum peptidome patterns
• SISCAPA method for quantitating proteins and peptides in plasma
• Comparison of proteomic profiling technologies for discovery of biomarkers
• Verification for interlaboratory reproducibility of protein biomarkers
• Significance of similar protein biomarkers in different tissues
• Glycomic technologies
• Metabolomic technologies
• Mass spectrometry-based kits for discovery of metabolic biomarkers in plasma
• 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
• Lipidomics
• Disease biomarkers in breath
• Portable breath test for volatile organic compounds
• Detection of breath biomarkers by sensation technology
• Detection of breath biomarkers optical frequency comb spectroscopy
• Fluorescent indicators for biomarkers
• Molecular imaging technologies
• Computer tomography
• Magnetic resonance imaging
• Positron emission tomography
• Advantages of imaging biomarkers
• Monitoring in vivo gene expression by molecular imaging
• Molecular imaging in vivo as a biomarker
• Challenges and future prospects of molecular imaging
• Basic research in molecular imaging
• Imaging intracellular NADH as a biomarker of disease
• Devices for molecular imaging
• Imaging biomarkers in clinical trials
• Molecular imaging in clinical practice
• Nuclear magnetic resonance
• Chemical derivatization to enhance biomarker detection by NMR
• Fluxomics by using NMR
• Nanobiotechnology
• Nanomaterials for biolabeling
• Quantum dot molecular labels
• Bioconjugated QDs for multiplexed profiling of biomarkers
• Magnetic nanotags for multipley detection of biomarkers
• Nanoproteomics and biomarkers
• High-field asymmetric waveform ion mobility mass spectrometry
• Nanoparticles for molecular imaging
• Nanoparticles for discovering biomarkers
• Nucleoprotein nanodevices for detection of cancer biomarkers
• Future prospects of application of nanobiotechnology for biomarkers
• Bioinformatics
• Biomarker Workflow Guide
• Analysis of microarray data for selecting useful biomarkers
• Role of bioinformatics in discovery of proteomic biomarkers
• Role of bioinformatics in detection of cancer biomarkers
• Biomarker databases
• Gene networks as biomarkers

3. Biomarkers and Molecular Diagnostics

• Introduction
• Molecular diagnostic technologies
• Polymerase chain reaction
• Amplification
• Target selection
• Detection of amplified DNA
• Limitations of PCR
• Real-time PCR systems
• Limitations of real-time PCR
• Future applications of real-time Q-PCR
• Combined PCR-ELISA
• Non-PCR methods
• Linked Linear Amplification
• Transcription mediated amplification
• Rapid analysis of gene expression
• WAVE nucleic acid fragment analysis system
• DNA probes with conjugated minor groove binder
• Rolling circle amplification technology
• Gene-based diagnostics through RCAT
• RCAT-immunodiagnostics
• RCAT-biochips
• RCAT-pharmacogenomics
• Circle-to-circle amplification
• Biochips and microarrays
• Applications of biochips/microarrays
• Role of biochip/microarrays in discovery of biomarkers
• Biomarkers and high throughput molecular screening
• Detection and expression profiling of miRNA
• Real-time PCR for expression profiling of miRNAs
• Real-time PCR for expression profiling of miRNAs
• Use of LNA to explore miRNA
• Microarrays for analysis of miRNA gene expression

4. Biomarkers for Drug Discovery & Development

• Introduction
• Biomarker technologies for drug discovery
• Proteomics-based biomarkers for drug discovery
• Chemoproteomics
• Transcriptomics for drug discovery
• Metabolomics for drug discovery
• Biomarkers and drug safety
• Biomarkers of adverse drug reactions
• Applications of biomarkers in drug safety studies
• Genomic technologies for toxicology biomarkers
• Proteomic technologies for toxicology biomarkers
• Metabonomic technologies for toxicology biomarkers
• Integration of genomic and metabonomic data to develop toxicity biomarkers
• Toxicology studies based on biomarkers
• Biomarkers of hepatotoxicity
• Biomarkers of nephrotoxicity
• Cardiotoxicity
• Neurotoxicity
• Applications of biomarkers for drug development
• Application of metabonomics/metabolomics for drug development
• Role of pharmacokinetic/pharmacodynamic biomarkers in drug development
• Molecular imaging as a biomarker in drug development
• Molecular imaging in preclinical studies
• Molecular imaging in clinical trials
• Prospects of molecular imaging in drug discovery and development
• Biomarkers in clinical trials
• NIH recommendations on the use of biomarkers in clinical trials
• Advantages of biomarkers for drug development
• Limitations and problems with use of biomarkers in clinical trials
• Application of biomarkers by the pharmaceutical companies
• Use of biomarkers in relation to stage of drug discovery and development
• Drug development in cardiovascular disorders
• Drug development in neurological disorders
• Future prospects of biomarker-based drug development
• The Biomarker Alliance
• Molecular Libraries and Imaging Roadmap of NIH
• Biomarkers Consortium

5. Role of Biomarkers in Healthcare

• Introduction
• Biomarkers of inflammation
• Biomarkers of oxidative stress
• Oxidative DNA damage
• Proteins as biomarkers of oxidative stress in diseases
• 1,4-dihydroxynonane-mercapturic acid
• Biomarkers in metabolic disorders
• Biomarkers of acute intermittent porphyria
• Liver X receptors
• Biomarkers of diabetes mellitus
• Biomarkers of hyperglycemia
• Biomarkers of diabetes-associated oxidative stress
• Biomarkers of inflammation associated with diabetes
• Biomarkers of renal complications in diabetes mellitus type 2
• Biomarkers of diabesity
• Glycosylated hemoglobin in diabetes mellitus
• Lack of C-peptide as biomarker of complications of diabetes type 1
• Serum retinol binding protein 4 as biomarker of insulin resistance
• Biomarkers of metabolic syndrome
• Adiponectin
• Biomarkers in immune disorders
• Biomarkers of failure of transplanted organs
• Immunological biomarkers of graft versus host disease
• Biomarkers of renal allograft failure
• Biomarkers of lung transplant rejection
• Systemic lupus erythematosus
• Current management and need for biomarkers
• Role of collaborative efforts and databases of SLE biomarkers
• C4d-bearing reticulocytes
• Adiponectin
• CB-CAPS
• Genetic loci of SLE
• Epigenetic biomarkers of SLE
• Biomarkers of musculoskeletal disorders
• Biomarkers of rheumatoid arthritis
• Biomarkers of spondylarthritis
• Biomarkers of osteoarthritis
• Biomarkers of osteoporosis
• Dual x-ray absorptiometry
• Bone imaging with quantitative CT and MRI
• Assays for detection of biomarkers of osteoporosis
• Biomarkers of infectious diseases
• Procalcitonin
• Endotoxin
• Chemokines as biomarkers of infection
• Circulating CPS-1 as biomarkers of organ damage in sepsis
• Application of proteomics for discovering biomarkers of infections
• Systemic inflammatory response syndrome
• Tuberculosis
• Conventional diagnosis of tuberculosis
• Molecular diagnostics for tuberculosis
• Biomarkers for tuberculosis
• Biomarkers of pulmonary tuberculosis in the breath
• Biomarkers of viral infections
• Viral hepatitis
• Biomarkers of SARS
• Biomarkers of HIV
• Biomarkers in parasitic infections
• Role of biomarkers in malaria
• Identification of biomarkers in Schistosomiasis infections
• Biomarkers of liver disease
• Breath biomarkers of liver disease
• Biomarkers of viral hepatitis B and C
• Biomarkers of liver injury
• Biomarkers of liver cirrhosis
• FibroMax
• Biomarkers of pancreatitis
• Biomarkers of renal disease
• Cystatin C as biomarker of glomerular filtration rate
• Proteomic biomarkers of acute kidney injury
• Biomarkers of lupus nephritis
• Biomarkers of diabetic nephropathy
• Biomarkers of pulmonary diseases
• Biomarkers of oxidative stress in lung diseases
• Biomarkers of survival in acute respiratory distress syndrome
• Urinary NO as biomarker
• Plasma biomarkers related to inflammation
• Pulmonary surfactant proteins as biomarkers for lung diseases
• Cytokine/chemokine biomarkers of SARS
• Biomarkers of chronic obstructive pulmonary disease
• Increased expression of PIGF as a biomarker of COPD
• Chromagranin A (CgA) as biomarker of airway obstruction in smokers
• BNP as a biomarker of chronic pulmonary disease
• Alpha1-antitrypsin gene polymorphisms predisposing to emphysema
• Biomarkers of asthma
• Comparison of biomarkers of asthma and COPD
• Exaled NO as a biomarker of asthma
• Cytokines as biomarkers of asthma severity
• Biomarker for rhinovirus-induced asthma exacerbation
• Biomarkers for predicting response to corticosteroid therapy
• IgE as guide to dosing of omalizumab for asthma
• Endothelin-1 in exhaled breath as biomarker of asthma
• Biomarkers for cystic fibrosis
• Biomarkers of pulmonary embolism
• Biomarkers in obstetrics and gynecology
• Biomarkers for preeclampsia
• Protein biomarker of preeclampsia in urine
• Protein biomarkers of preeclampsia in CSF
• Protein HtrA1 as biomarker for preeclampsia
• sFlt1 and soluble endoglin as biomarkers of preeclampsia
• RNA biomarkers
• Biomarkers of premature birth
• Biomarkers of oxidative stress in complicated pregnancies
• Biomarkers of premenstrual dysphoric disorder
• Biomarkers of endometriosis
• Fetal biomarkers in maternal blood
• Biomarkers for genetic disorders
• Biomarkers for Down' s syndrome
• Biomarkers for muscular dystrophy
• Biomarkers of phenylketonuria
• Genetic biomarkers for psoriasis
• Biomarkers of lysosomal storage disorders
• Biomarkers of aging
• Study of biomarkers of aging in a genetically homogeneous population
• Genes as biomarkers of aging
• Telomere attrition as aging biomarker
• Mitochondrial mutations as biomarkers of aging
• Role of bioinformatics in search for biomarkers of aging
• Effect of calorie restriction on biomarkers of longevity
• Biomarkers of miscellaneous disorders
• Biomarkers of inflammatory bowel disease
• Biomarkers of erectile dysfunction
• Biomarkers of heat stroke
• Biomarkers of pain
• Biomarkers of neuropathic pain
• Brain insular glutamate as biomarker of fibromyalgia
• Biomarkers of visceral pain
• Nasal nitric oxide as a biomarker of response to rhinosinusitis therapy
• Biomarkers common to multiple diseases
• Biomarkers and nutrition
• Biomarkers in nutritional epidemiology
• Biomarkers of nutritional status
• Biomarkers of branched chain amino acid status
• Biomarkers of caloric restriction
• Biomarkers of malnutrition
• Proteomic biomarkers and nutrition
• Biomarkers of gene-environmental interactions in human disease

6. Biomarkers of Cancer

• Introduction
• The ideal biomarker for cancer
• Single vs multiple biomarkers of cancer
• Types of cancer biomarkers
• miRNAs as biomarkers in cancer
• Circulating miRNAs for cancer detection
• Diagnostic value of miRNA in cancer
• Biomarkers of epigenetic gene silencing in cancer
• Immunologic biomarkers of cancer
• Molecular diagnostic techniques for cancer
• Technologies for detection of cancer biomarkers
• Genomic technologies for cancer biomarkers
• Cold-PCR
• Genome analysis at the molecular level
• Sequencing-based approaches for detection of cancer biomarkers
• Early detection of tumor suppressor gene mutations
• Biomarkers of PTEN tumor suppressor gene status
• HAAH as a biomarker for cancer
• Telomerase as a biomarker of cancer
• Digital karyotyping for cancer biomarkers
• LigAmp for detection of gene mutations in cancer
• Mitochondrial DNA as a cancer biomarker
• Tissue microarrays for study of cancer biomarkers
• Molecular fingerprinting of cancer
• Biomarkers of inflammation in cancer
• Proteomic technologies for detecting biomarkers of cancer
• 2D PAGE
• Antibody-based detection of protein biomarkers
• Aptamer-based molecular probes for cancer biomarker discovery
• Cancer immunomics to identify autoantibody signatures
• Desorption electrospray ionization for detection of cancer biomarkers
• Detection of circulating nucleosomes in serum of cancer patients
• Detection of tumor markers with ProteinChip technology
• eTag assay system for cancer biomarkers
• Glycoprotein biomarkers of cancer
• HER-2/neu oncoprotein as biomarkers for cancer
• Humoral proteomics
• Laser capture microdissection
• Phage display technology
• Proteomic analysis of cancer cell mitochondria
• Proteomic technologies for detection of autoimmune biomarkers
• SELDI-TOF MS
• Serum proteome analysis for early detection of cancer
• Tissue proteomics for discovery of cancer biomarkers
• Metabolomic biomarkers of cancer
• Choline phospholipid biomarkers of cancer
• Hypoxia-inducible factor-1
• Detection of drug resistance in cancer by metabolic profiling
• Epitomics for the early detection of cancer
• Detection of biomarkers of DNA methylation
• PCR with bisulfite for detecting DNA methylation biomarkers in cancer
• MDScan™ microarray technology
• Rubicon MethylPlex technology
• Epigenomics Marker Machine for DNA methylation biomarkers
• Sequenom' s integrated genetic analysis platform
• Histone deacetylase
• Mucins as epigenetic biomarkers in epithelial cancers
• Nanobiotechnology for early detection of cancer to improve treatment
• Selective expression of biomarkers by cancer compared with normal tissues
• Ultrasound radiation to enhance release of a tumor biomarker
• In vivo imaging of cancer biomarkers
• Computer tomography
• Optical systems for in vivo molecular imaging of cancer
• Positron emission tomography
• Imaging of tumor oxygenation and microvascular permeability by MRI
• Xenon-enhanced MRI
• Kallikrein gene family and cancer biomarkers
• Circulating cancer cells in blood as biomarkers of cancer
• Applications of cancer biomarkers
• Use of biomarkers for cancer classification
• Cancer classification using microarrays
• Proteomic classification of cancer
• Use of biomarkers for early detection of cancer
• Applications of biomarkers for cancer diagnosis
• Methylated DNA sequences as cancer biomarkers
• MicroRNA expression profiling for diagnosis of human cancers
• MUC4 as a diagnostic biomarker in cancer
• Applications of biomarkers for cancer diagnosis and therapy
• Asparagine synthetase as biomarker for therapy with L-asparaginase
• Peptide-based agents for targeting cancer biomarkers
• Biomarkers for assessing efficacy of cancer therapy
• ERCC1-XPF expression as a biomarker of response to chemotherapy
• GRP78 as a predictor for chemoresponsiveness of breast cancer
• HtrA1 as a biomarker of response to chemotherapy in ovarian cancer
• P53 expression level as biomarker of efficacy of cancer gene therapy
• Biomarkers of angiogenesis for developing antiangiogenic therapy
• Tumor endothelial markers
• Circulating endothelial cells as targets for antiangiogenic drugs
• Biomarkers of response to antiangiogenic agent brivanib alaninate
• DCE-MRI biomarkers for evaluation of antiangiogenic agents
• Combination of soluble biomarkers of angiogenesis with imaging
• Biomarkers of drug resistance in cancer
• A systems approach to biomarkers of innate drug resistance
• Epithelial membrane protein-1 as a biomarker of gefitinib resistance
• Methylation biomarkers of drug resistance in cancer
• Biomarkers of radiation exposure
• Role of biomarkers in drug development in oncology
• Molecular imaging of tumor as a guide to drug development
• Use of PET to assess response to anticancer drugs
• Use of MRI to assess response to anticancer drugs
• Biomarkers in plucked hair for assessing cancer therapy
• Molecular targets of anticancer drugs as biomarkers
• Safety biomarkers in oncology studies
• Role of biomarkers in phase I clinical trials of anticancer drugs
• Biomarkers according to location/type of cancer
• Bladder cancer biomarkers
• Urinary telomerase as biomarker for detection of bladder cancer
• Brain cancer biomarkers
• Biomarkers to predict response to EGFR inhibitors
• CD133 as biomarker of resistance to radiotherapy
• Circulating microvesicles as biomarkers
• CSF protein profiling
• CSF attractin as a biomarker of malignant astrocytoma
• Methylation profiling of brain tumors
• Metabolite biomarkers of brain tumors
• miRNA biomarker of brain tumors
• MRI biomarker for response of brain tumor to therapy
• Neuroimaging biomarkers combined with DNA microarray analysis
• Receptor protein tyrosine phosphatase β as biomarker of gliomas
• Serum protein fingerprinting
• Breast cancer biomarkers
• Biomarkers of breast cancer in breath
• Biomarkers for breast cancer in nipple aspiration fluid
• Decreased breast density as a biomarker of response to tamoxifen
• Flow cytometry for quantification of biomarker expression patterns
• Plasma proteomics for biomarkers of breast cancer
• Quantitative realtime PCR assays for biomarker validation
• Cdk6 as a biomarker of breast cancer
• Centromere protein-F
• Carbonic anhydrase IX
• COX-2 as a biomarker of breast cancer
• Glycomic biomarkers of breast cancer
• HER-2/neu oncoprotein
• High mobility group protein A2
• Lipocalin 2 as biomarker of breast cancer progression
• Mammaglobin
• p27 expression as biomarker for survival after chemotherapy
• Podocalyxin
• Progranulin as a biomarker of breast cancer
• Proliferating cell nuclear antigen
• Protein kinase C as a predictive biomarker of metastatic breast cancer
• Retinoblastoma tumor suppressor gene as a biomarker
• Riboflavin carrier protein
• Serum CA 15-3 as biomarker of prognosis in advanced breast cancer
• Suppressor of deltex protein
• Tumor microenvironment as biomarker of metastasis in breast cancer
• Type III TGF-β receptor as regulator of cancer progression
• Diagnostic tests based on breast cancer genes
• Prognostic role of breast cancer genes
• Protein biomarkers for breast cancer prevention
• Biomarkers to evaluate efficacy of chemoprevention
• Biomarker prognosis of breast cancer treated with doxorubicin
• Cervical cancer biomarkers
• Gastrointestinal cancer biomarkers
• Gastric cancer biomarkers
• Colorectal cancer biomarkers
• Head and neck cancer
• Leukemia biomarkers
• Chromosome translocations in leukemias
• DNA methylation biomarkers in leukemia
• Gene mutations as biomarkers in leukemia
• Molecular diagnostic techniques for leukemia
• Proteomic technologies for discovering biomarkers of leukemia
• Biomarkers of chronic lymphocytic leukemia
• Biomarkers of chronic myeloid leukemia
• Biomarkers of drug resistance in leukemia
• Biomarkers of myelodysplasitic syndromes
• Liver cancer biomarkers
• Lung cancer biomarkers
• Autoantibodies as biomarkers in lung cancer
• Biomarkers associated with neuroendocrine differentiation in NSCLC
• Biomarkers of chronic inflammation in lung cancer
• Biomarkers for predicting sensitivity to chemotherapy in lung cancer
• Biomarkers for prediction of sensitivity to EGFR inhibitors
• Circulating tumor cells as biomarkers
• Gene expression profiling for biomarkers of lung cancer
• Methylation biomarkers of lung cancer
• miRNA biomarkers in lung cancer
• Proteomic biomarkers in exaled breath condensate
• Serum protein biomarkers of lung cancer
• tNOX as biomarker of lung cancer
• Tumor-derived DNA and RNA markers in blood
• Volatile organic compounds in the exhaled breath
• Malignant pleural mesothelioma
• Melanoma biomarkers
• Nasopharyngeal carcinoma biomarkers
• Proteomic biomarkers of nasopharyngeal cancer
• miRNA biomarkers of nasopharyngeal carcinoma
• Oral cancer biomarkers
• Ovarian cancer biomarkers
• Gene exprression studies
• Mutation of genes
• Serum CA-125 as biomarker of ovarian cancer prognosis
• Serum albumin-associated peptides and proteins
• Multiplex assays for biomarkers of ovarian cancer
• Epitomics approach for ovarian cancer biomarkers in serum
• Concluding remarks on biomarker-based tests of ovarian cancer
• Pancreatic cancer biomarkers
• Discovery and validation of pancreatic cancer biomarkers
• Cancer stem cells as biomarkers of pancreatic cancer
• miRNA biomarkers of pancreatic cancer
• Proteomic biomarkers of pancreatic cancer
• Prostate cancer
• Adipose tissue-derived biomarkers of obesity-related prostate cancer
• B7-H3 as biomarker of prostate cancer
• Detection of prostate cancer biomarkers in urine
• Detection of prostatic intraepithelial neoplasia
• Epigenetic biomarkers of prostate cancer
• Genetic biomarkers of prostate cancer
• Huntingtin Interacting Protein 1 overexpression in prostate cancer
• Id proteins expression in prostate cancer
• Identification of prostate cancer mRNA biomarkers
• Integrative genomic and proteomic profiling of prostate cancer
• LCM for diagnosis of prostate cancer
• Loss of p27 as predictor of recurrence of prostate cancer
• Microarray for diagnosis of prostate cancer
• miRNA biomarkers of prostate cancer
• Prostate cancer biomarkers in semen
• PSA as biomarker of prostate cancer
• PSMA as biomarker of prostate cancer
• Serum HAAH as biomarker of prostate cancer
• Silenced CDH13 gene as a biomarker of cancer
• Serum-protein fingerprinting
• Tests for prostate cancer based on genetic dislocations
• Concluding remarks on biomarkers of prostate cancer
• Renal cancer biomarkers
• Gene expression profile of RCC for biomarkers
• miRNA biomarkers of renal cancer
• Use of proteomics for detection of RCC biomarkers
• Use of RCC biomarkers for prognosis and therapy
• Thyroid cancer biomarkers
• Gene expression biomarkers of thyroid cancer
• Multiple endocrine neoplasia type 2B as risk factor for thyroid cancer
• miRNA biomarkers of thyroid cancer
• Biochemical biomarkers of thyroid cancer
• Role of the NCI in molecular diagnosis of cancer
• The Cancer Genome Anatomy Project
• Molecular profiling of cancer
• Cancer Genome Atlas
• Cancer Genetic Markers of Susceptibility Project
• Oncology Biomarker Qualification Initiative
• Role of NCI in cancer biomarker development and validation
• COBRED project for cancer biomarker research in Europe
• Future prospects for cancer biomarkers
• Cancer biomarker research at academic institutions
• Future prospects and challenges in the discovery of cancer biomarkers

7. Biomarkers of Disorders of the Nervous System

• Introduction
• Discovery of biomarkers for neurological disorders
• Biomarker identification in the CSF using proteomics
• Biomarker identification in the CSF using lipidomics
• Cerebral microdialysis for the study of biomarkers of cerebral metabolism
• Detection of protein biomarkers of CNS disorders in the blood
• Brain imaging for detection of biomarkers
• Data mining for biomarkers of neurological disorders
• Antibodies as biomarkers in disorders of the nervous system
• Biomarkers of neural regeneration
• Biomarkers of disruption of blood-brain barrier
• Biomarkers of neurotoxicity
• Glial fibrillary acidic protein as biomarker of neurotoxicity
• Single-stranded DNA as a biomarker of neuronal apoptosis
• Biomarkers of neurodegenerative disorders
• Biomarkers of Alzheimer' s disease
• The ideal biomarker for AD
• Protein biomarkers of AD in CSF
• Amyloid precursor protein
• Tau proteins in CSF
• Tests for the detection of Aβ in CSF
• Monitoring of synthesis and clearance rates ofAβ in the CSF
• Tests combining CSF tau and Aβ
• CSF sulfatide as a biomarker for AD
• Glycerophosphocholine as CSF biomarker in AD
• CSF Reelin as biomarker of AD
• Urine tests for AD
• Blood tests for AD
• Protein kinase C in red blood cells
• Detection of aggregated misfolded proteins in the blood
• Lymphocyte Proliferation Test
• A biomarker-based skin test for AD
• Radioiodinated clioquinol as a biomarker for Aβ
• Nanotechnology to measure Aβ derived diffusible ligands
• Simultaneous measurement of several biomarkers for AD
• Use of biomarkers to predict AD in patients with MCI
• Genetic tests for AD
• Gene expression patterns in AD
• Magnetic resonance spectroscopy in AD
• MRI for biomarkers of AD
• PET scanning for biomarkers of AD
• Targeting of chemokine receptor as biomarker for brain imaging
• Plasma biomarkers of drug response in AD
• Concluding remarks about biomarkers for AD
• Biomarkers of Parkinson' s disease
• Biochemical biomarkers of PD
• Biomarkers of PD based on gene expression in blood
• Cardiac denervation as a biomarker of PD
• Imaging biomarkers of PD
• Metabolic brain networks as biomarkers
• Metabonomic biomarker profile for diagnosis and monitoring of PD
• Future prospects for biomarkers of PD
• Biomarkers of Huntington' s disease
• Quantitative MRI measurement of brain atrophy as biomarker of HD
• Biomarkers of Wilson' s disease
• Biomarkers of amyotrophic lateral sclerosis
• Biomarkers of neuroinflammation in ALS
• Detection of ALS biomarkers in blood vs CSF
• Ideal biomarker of ALS
• Imaging biomarkers of ALS
• Metabolomic biomarkers of ALS
• Proteomic biomarkers of ALS
• Future prospects of biomarkers of ALS
• Biomarkers of dementia in HIV-1-infected patients
• Biomarkers of prion diseases
• 14-3-3 protein and tTau/P-Tau ratio
• Bioluminescence imaging as a surrogate biomarker of prion infectivity
• Biomarkers of multiple sclerosis
• Antibodies in multiple sclerosis
• Antibodies to galactocerebroside
• Antibodies to myelin oligodendrocyte glycoprotein
• Detecting autoantibodies in multiple sclerosis
• CSF Cystatin C as a biomarker of multiple sclerosis
• T cells as biomarkers of multiple sclerosis
• Matrix metalloproteinases as biomarkers in multiple sclerosis
• Gelsolin as a biomarker of multiple sclerosis
• Gene expression profiling of biomarkers in multiple sclerosis
• Serum proteomic pattern analysis in multiple sclerosis
• Biomarkers of remyelination and repair
• Myelin imaging by PET
• Biomarkers of response to therapy of multiple sclerosis
• Concluding remarks and future perspective for biomarkers of multiple sclerosis
• Biomarkers of stroke
• Biomarkers of intracerebral hemorrhage
• Biomarkers of hypoxic brain damage
• Brain natriuretic peptide as a biomarker for cardioembolic stroke
• Brain lactate and N-acetylaspartate as biomarkers of stroke
• Intercellular adhesion molecule 1 as biomarker of ischemic stroke
• Lp-PLA2 and CRP as biomarkers for stroke
• Neuroserpin polymorphisms as a biomarker of stroke
• NMDA receptors as biomarkers of excitotoxicity in stroke
• Nucleosomes as biomarkers of stroke
• PARK7 and nucleoside diphosphate kinase A as biomarkers of stroke
• Visinen-like protein 1
• Gene expression in blood following ischemic stroke
• Future prospects for biomarkers of stroke
• Biomarkers of traumatic brain injury
• Technologies for identification of biomarkers of TBI
• Proteomic technologies for biomarkers of TBI
• Cerebral microdialysis for study of biomarkers of TBI
• Biomarkers of TBI
• C-tau as biomarker of TBI
• Hyperphosphorylated axonal neurofilament protein
• IL-6 and nerve growth factor as biomarkers of TBI
• Serum S100B as biomarker of TBI
• Biomarkers of inflicted TBI in infants
• Clinical applications of biomarkers of TBI
• Biomarkers of CNS infections
• Biomarkers of CNS HIV infection
• Biomarkers of bacterial meningitis
• Biomarkers of epilepsy
• Genetic epilepsies
• Biochemical markers of epilepsy
• Imaging biomarkers of epilepsy
• Biomarkers of normal pressure hydrocephalus
• Biomarkers of retinal disorders
• Biomarkers of age-related macular degeneration
• Biomarkers for autism
• Biomarkers of sleep disorders
• Biomarker of excessive daytime sleepiness
• Biomarkers of obstructive sleep apnea
• Biomarkers of restless legs syndrome
• Biomarkers of psychiatric disorders
• Biomarkers of depression
• Biomarkers of psychosis
• Biomarkers of schizophrenia
• Genetic biomarkers of schizophrenia
• Gene expression analysis of blood for biomarkers of schizophrenia
• Proteomic studies for biomarkers of schizophrenia
• Metabolic biomarkers of schizophrenia

8. Biomarkers of Cardiovascular Disorders

• Introduction
• Epidemiology of cardiovascular disease
• Biomarkers of cardiovascular diseases
• Genetic biomarkers of cardiovascular disorders
• Methods for identification of cardiovascular biomarkers
• Application of proteomics for biomarkers of cardiovascular disease
• Detection of biomarkers of myocardial infarction in saliva by a nanobiochip
• Metabolomic technologies for biomarkers of myocardial ischemia
• Imaging biomarkers of cardiovascular disease
• Cardiovascular MRI
• Annexin A5 as an imaging biomarker of cardiovascular disease
• Applications of biomarkers of cardiovascular disease
• Biomarkers for ischemic heart disease and myocardial infarction
• Troponin
• Natriuretic peptide
• Creatine kinase muscle brain
• Myoglobin
• Fatty acid binding protein
• Cripto-1 as a biomarker of myocardial infarction
• Cataract as a biomarker of ischemic heart disease
• Plasma fetuin-A levels and the risk of myocardial infarction
• Biomarkers of congestive heart failure
• Angiogenesis biomarkers
• beta-2a protein as a biomarker of heart failure
• Galectin-3 as biomarker of acute heart failure
• G protein-coupled receptor kinase-2 as biomarker of CHF
• KIF6 gene as biomarker of CHF
• NT ProBNP as biomarker of CHF
• Oxidative stress as biomarker of heart failure
• Future prospects for biomarkers of heart failure
• Biomarkers for atherosclerosis
• Adipocyte enhancer-binding protein 1
• Ghrelin as a biomarker of atherosclerosis
• Imaging biomarkers of hypercholesterolemia/atherosclerosis
• Inflammatory biomarkers of atherosclerosis
• Lipid-modified proteins as biomarkers of atherosclerosis
• Lp-PLA2 as biomarker of atherosclerotic heart disease
• Nitric oxide impairment and atherosclerosis
• Oxygen free radicals as biomarkers of atherosclerosis
• Proteomic profiles of serum inflammatory markers of atherosclerosis
• Biomarkers of risk factors for coronary heart disease
• Antibody to oxidized-LDL
• Apolipoproteins as risk factors for coronary heart disease
• CRP as biomarker of risk for coronary heart disease
• Impairment of EPCs by oxidative stress as a biomarker of disease
• Biomarkers for pulmonary arterial hypertension
• Biomarkers of abdominal aortic aneurysm
• Genetic biomarkers for cardiovascular disease
• Genetic biomarkers of atherosclerosis
• IL-1 gene polymorphism as biomarker of cardiovascular disease
• Polymorphisms of the eNOS gene and angina pectoris
• Polymorphisms in the apolipoprotein E gene
• Mutations in the low density lipoprotein receptor gene
• Mutations within several genes that code for ion channel
• Polymorphism in the angiotensinogen gene
• Kallikrein gene mutations in cardiovascular disease
• Kallikrein gene and essential hypertension
• Gene mutations in pulmonary arterial hypertension
• Genetic biomarkers of early onset myocardial infarction
• Gene variant as a risk factor for sudden cardiac death
• Multiple biomarkers for prediction of death from cardiovascular disease
• Role of biomarkers in the management of cardiovascular disease
• Role of biomarkers in the diagnosis of myocardial infarction
• Role of biomarkers in the prevention of cardiovascular disease
• Molecular signature analysis in management of cardiovascular diseases
• C-reactive protein as biomarker of response to statin therapy
• Role of circulating biomarkers and mediators of cardiovascular dysfunction
• Use of biomarkers in the management of peripheral arterial disease
• Use of biomarkers in the management of hypertension
• Use of protein biomarkers for monitoring acute coronary syndromes
• Use of multiple biomarkers for monitoring of cardiovascular disease
• Future prospects for cardiovascular biomarkers
• Cardiovascular Biomarker Consortium
• Systems Approach to Biomarker Research in Cardiovascular Disease

9. Biomarkers & Personalized Medicine

• Introduction
• Pharmacogenetics
• Biomarkers and pharmacogenetics
• Pharmacogenomics
• Pharmacoproteomics
• Single cell proteomics for personalized medicine
• Role of biomarkers in development of personalized drugs
• Use of biomarkers for developing MAb therapy in oncology
• Biobanking, biomarkers and personalized medicine in EU
• Expression signatures as diagnostic/prognostic tools
• Biomarkers for monitoring response to therapy
• Drug rescue by biomarker-based personalized medicine
• Future role of biomarkers in personalized medicine

10. Regulatory issues

• Introduction
• Biomarker validation
• FDA criteria for a valid biomarker
• Role of NIST in validation of cancer biomarkers
• Quality specifications for BNP and NT-proBNP as cardiac biomarker assays
• FDA perspective of biomarkers in clinical trials
• FDA and predictive medicine
• Biomarkers and FDA' s Voluntary Genomic Data Submission
• Role of imaging biomarkers in approval of drugs
• FDA Critical Path Initiative and biomarker R&D
• FDA consortium linking genetic biomarkers to serious adverse events
• Oncology Biomarker Qualification Initiative
• Critical Path Initiative
• Predictive Safety Testing Consortium
• From validated biomarker assay to a clinical laboratory diagnostic
• Fast Path programs
• Need for a single federal agency to oversee biomarker field

11. Markets for Biomarkers

• Introduction
• Biomarker markets according to technologies/applications
• Markets for protein biomarkers
• Biomarker market relevant to drug discovery and development
• Biomarker market relevant to epigenetics
• Biomarket market relevant to bioinformatics
• Biomarker markets according to therapeutic areas
• Geographical distribution of biomarker markets
• Unfulfilled needs in biomarkers
• Drivers for the growth of markets for biomarkers
• Challenges facing the biomarker industry
• Pitfalls in the discovery and development of biomarkers
• Strategies for developing biomarker markets
• Utilization of biomarker research in academic laboratories
• Biomarker discovery at pharmaceutical companies
• Industrial-academic collaborations in biomarkers
• Application of biomarkers in medical practice
• Future role of biomarkers in healthcare
• Applications of biomarkers beyond healthcare
• Combating bioterrorism
• Biomarkers for monitoring human exposure to environmental toxins
• Application of biomarkers in animal health
• Biomarker patents
• Factors that enhance the value of biomarker IP
• US policy on gene patenting relevant to biomarkers

12. References

Tables

• Table 1 1: Historical landmarks in discovery and development of biomarkers
• Table 1 2: Classification of biomarkers
• Table 1 3: Terminology of biomarkers of disease relevant to clinical development
• Table 1 4: Autoimmune disorders under study for autoantibodies as predictors
• Table 1 5: Use of “-omic” technologies for discovery of biomarkers
• Table 1 6: Role of biomarkers in translational medicine
• Table 2 1: Classification of methods of gene expression analysis
• Table 2 2: Comparison of proteomic profiling technologies for discovery of biomarkers
• Table 2 3: Companies involved in developing molecular imaging
• Table 3 1: Applications of biochip/microarray technology in relation to biomarkers
• Table 4 1: Companies using metabolomics for drug discovery
• Table 4 2: Causes of failures in clinical trials and their reduction by use of biomarkers
• Table 4 3: Biomarker-based drug development at major pharmaceutical companies
• Table 5 1: Biomarkers of diabetes mellitus
• Table 5 2: Biomarkers of sepsis
• Table 5 3: Biomarkers of pulmonary diseases
• Table 5 4: Biomarkers of aging
• Table 5 5: Examples of biomarkers common to multiple diseases
• Table 6 1: Desirable characteristics of biomarkers for cancer
• Table 6 2: Types of cancer biomarkers
• Table 6 3: A classification of molecular diagnostic methods in cancer
• Table 6 4: Biomarkers of brain tumors
• Table 6 5: Biomarkers of breast cancer
• Table 6 6: Biomarkers of colorectal cancer
• Table 6 7: Biomarkers of lung cancer
• Table 6 8: Classification of biomarkers of melanoma
• Table 6 9: Biomarkers of nasopharyngeal carcinoma and potential applications
• Table 6 10: Biomarkers of ovarian cancer
• Table 6 11: Classification of biomarkers of pancreatic cancer
• Table 6 12: Biomarkers of prostate cancer
• Table 7 1: Biomarkers of cerebral metabolism
• Table 7 2: Classification of biochemical markers of AD in blood and CSF
• Table 7 3: Characteristics of an ideal biomarker for Alzheimer disease
• Table 7 4: Biomarkers of Parkinson' s disease
• Table 7 5: Classification of biomarkers of sporadic amyotrophic lateral sclerosis
• Table 7 6: Biomarkers of multiple sclerosis
• Table 7 7: Biomarkers of response to interferon-b in multiple sclerosis
• Table 7 8: Biomarkers of stroke
• Table 7 9: Biochemical biomarkers of traumatic brain injury
• Table 7 10: Biomarkers of epilepsy
• Table 8 1: Classification of biomarkers for cardiovascular diseases
• Table 8 2: Genes that cause cardiovascular diseases
• Table 9 1: Pharmacogenetic vs. pharmacogenomic studies
• Table 9 2: Applications of pharmacoproteomic biomarkers in personalized medicine
• Table 11 1: Biomarker markets according to technologies/applications 2008-2018
• Table 11 2: Biomarker markets according to therapeutic areas 2008-2018
• Table 11 3: Geographical distribution of biomarker markets 2008-2018
• Table 11 4: Factors driving the growth of biomarker industry

Figures

• Figure 1 1: Relation of biomarkers to other technologies and healthcare
• Figure 2 1: The central role of spectrometry in proteomics
• Figure 4 1: Role of biomarkers in drug discovery and development process
• Figure 6 1: Role of proteomics in the discovery of cancer biomarkers
• Figure 6 2: Cancer biomarker development and validation
• Figure 7 1: Discovery and application of biomarkers in neurological diseases
• Figure 9 1: Role of pharmacogenetic biomarkers in personalized medicine
• Figure 9 2: Impact of biomarkers on personalized medicine
• Figure 10 1: Stages and timelines of biomarker discovery, development and marketing
• Figure 10 2: Biomarker qualification pilot process at the FDA
• Figure 10 3: From a validated biomarker assay to a clinical laboratory diagnostic
• Figure 11 1: Unfulfilled needs in biomarkers technologies and applications