The Future Of Personalized Medicine: The Impact Of Proteomics On Drug Discovery And Clinical Trial Design

Published by: Business Insights

Published: Oct. 1, 2004 - 157 Pages

Table of Contents

• Executive summary
  
• Introduction to proteomics
  
• Proteomic technologies
  
• Proteomic applications in drug discovery
  
• Proteomic applications in clinical trial design and personalized medicine
  
• Pharma and proteomic company alliances

Chapter 1 Introduction to proteomics

• Summary
  
• Introduction
  
• The human genome versus the proteome
  
• Identification of human genome
  
• Applications to proteomics
  
• The relationship between the proteome and the genome
  
• The genome
  
• Proteins
  
• From genes to proteins
  
• Proteomics
  
• Conclusions

Chapter 2 Proteomic technologies

• Summary
  
• Laboratory methods used in proteomics
  
• Separation techniques
  
• Identification techniques
  
• Interactions techniques
  
• Separation techniques
  
• 2-dimensional polyacrylamide gel electrophoresis (2-D PAGE)
  
• Liquid chromatography (LC)
  
• Protein arrays
  
• Identification techniques
  
• Mass spectrometry
  
• Protein-protein interaction techniques
  
• Automation
  
• Pre-fractionation
  
• Separation
  
• Identification
  
• Complete proteomics solutions
  
• The future of automation in proteomics
  
• Conclusions
  
• Bioinformatics and databases
  
• Data analysis
  
• Databases
  
• Laboratory information management systems (LIMS)
  
• Conclusions
  
• Overall conclusions

Chapter 3 Proteomic applications in drug

• discovery
  
• Summary
  
• Introduction
  
• Optimizing the R&D process
  
• Early selection of efficacious and non-toxic drug targets
  
• Toxicoproteomics
  
• Pharmacoproteomics
  
• Conclusions
  
• Accelerating the discovery of new targets for therapeutic candidates
  
• Therapeutic proteins
  
• Protein targets
  
• Mining the proteome is an alternative approach for drug discovery
  
• Conclusions

Chapter 4 Proteomic applications in clinical
trial design and personalized

• medicine
  
• Summary
  
• Development of new biomarkers
  
• Biomarkers as clinical endpoints
  
• Responders and non-responders
  
• Patients with adverse reactions
  
• Patients in different stages of a disease, or other subsets of patients
  
• Monitor clinical responses in new and comparator drugs - allowing potential
  
• strategic alliances
  
• Patients with disease resistance
  
• Niche markets
  
• Conclusions
  
• Application of biomarkers by therapy area
  
• Oncoproteomics
  
• Application in the diagnosis of ovarian cancer
  
• Application in the diagnosis of prostate cancer
  
• Application in the diagnosis of breast cancer
  
• Application in the diagnosis of esophageal cancer
  
• Neuroproteomics
  
• Application in the diagnosis of Alzheimer’s diseases
  
• Application in the diagnosis of amyotrophic lateral sclerosis (ALS)
  
• Cardioproteomics
  
• Cardiovascular markers
  
• Respiratory markers
  
• Application in organ transplantation
  
• Post-marketing applications of biomarkers
  
• Conclusions
  
• Conclusions
  
• Conclusions

Chapter 5 Pharmaceutical and proteomic

• company alliances
  
• Summary
  
• Introduction
  
• Recent collaborations and alliances of pharma and proteomic based
  
• companies
  
• Abbott
  
• AstraZeneca
  
• Aventis
  
• Bayer
  
• Bristol-Myers Squibb
  
• Boehringer Ingleheim
  
• Daiichi
  
• Eli Lilly
  
• Fujisawa
  
• GlaxoSmithKline
  
• Johnson & Johnson
  
• Lundbeck
  
• Merck & Co.
  
• Conclusions

Chapter 6 Appendix

• 2-dimensional polyacrylamide gel electrophoresis (2-D PAGE)
  
• Summary
  
• Liquid chromatography (LC)
  
• Gel filtration chromatography
  
• Ion exchange chromatography
  
• Affinity chromatography
  
• Partitioning chromatography
  
• LC summary
  
• High performance liquid chromatography
  
• Protein arrays
  
• Expression arrays
  
• Functional arrays
  
• Reverse arrays
  
• Protein array summary
  
• Mass spectrometry (MS)
  
• Electro-spray ionization
  
• Laser desorption/ionization
  
• MALDI
  
• SELDI
  
• Protein-protein interactions
  
• Fluorescence resonance energy transfer
  
• Bioinformatics databases
  
• Summary
  
• Sequence databases and alignment tools
  
• Domain and 3-dimensional structure databases
  
• Databases of biochemical pathways
  
• ‘Techniques’ databases
  
• The human proteome organization
  
• Index
  
• References
  
• Website references

List of Figures

• Figure 1.1: Nearly 500 proteins identified through proteomics have known functions in disease
  
• Figure 1.2: The basic structure of the (unwound) DNA helix
  
• Figure 1.3: The general structure of an amino acid and peptide bond
  
• Figure 1.4: The active site of the bacterial serine protease subtilisin
  
• Figure 1.5: The process of protein synthesis
  
• Figure 2.6: Techniques used in proteomics
  
• Figure 2.7: The role and scope of bioinformatics in proteomics research
  
• Figure 3.8: Only 30% of drugs produce revenues that exceed the average R&D cost
  
• Figure 3.9: Industry average attrition curves, 2004
  
• Figure 3.10: US pharmaceutical industry R&D expenditure and NCEs approvals, 1995-2003
  
• Figure 3.11: Strategies for analysis of toxicoproteomic data
  
• Figure 3.12: The impact of protein probes on drug discovery
  
• Figure 4.13: Three stages of diagnostic development
  
• Figure 4.14: The predicted individual response to any one drug
  
• Figure 6.15: Example of a 2-D PAGE gel
  
• Figure 6.16: Representation of liquid chromatography
  
• Figure 6.17: Typical high performance liquid chromatography set-up
  
• Figure 6.18: Representation of a ‘sandwich’ - type expression array
  
• Figure 6.19: A typical ESI instrument set up
  
• Figure 6.20: Simplified diagram of MALDI apparatus
  
• Figure 6.21: Representation of the yeast two hybrid system
  
• Figure 6.22: Schematic representation of FRET for investigating protein-protein interactions
  
• Figure 6.23: Representation of FRET for investigating protein-protein interactions
  
• Figure 6.24: Example of a pathway diagram from KEGG

List of Tables

• Table 1.1: The single- and three-letter amino acid codes
  
• Table 1.2: The codons and the amino acids that they specify
  
• Table 2.3: Summary of key proteomics technologies
  
• Table 2.4: A selection of protein array manufacturers*
  
• Table 2.5: Automation of proteomic platforms
  
• Table 2.6: Summary of proteomics databases*
  
• Table 3.7: Constant dollar reduction in total cost per new drug, 2002
  
• Table 3.8: R&D spend on drug development, 2002
  
• Table 3.9: New biologics
  
• Table 3.10: Recombinant proteins
  
• Table 3.11: Protein drug targets
  
• Table 3.12: New proteomic targets
  
• Table 4.13: Proteomic biomarkers
  
• Table 4.14: Correlation of survival with HER-2 over-expression
  
• Table 5.15: Colloborations implementing proteomics technologies

Abstract

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