Biomarker Technology Platforms for Cancer Diagnoses and Therapies

Table of Contents

1. Overview

• 1.1 Statement of Report
• 1.2 About This Report
• 1.3 Scope of the Report
• 1.4 Objectives
• 1.5 Methodology
• 1.6 Executive Summary

2. Introduction to Cancer Biology and the Diagnostic Industry

• 2.1 Biomarkers
  • 2.1.1 The Biomarker Market Drivers
    • 2.1.1.1 The Sector
    • 2.1.1.2 The Critical Path Opportunities
    • 2.1.1.3 The Capital Markets
• 2.2 Cancer Detection and Treatment with Biomarkers
  • 2.2.1 The Problem
• 2.3 Cancer: The Disease
  • 2.3.1 Metastasis
  • 2.3.2 Demographics and Statistics of Cancer
• 2.4 Drivers of the Biotech and Diagnostics Industry
  • 2.4.1 Venture Funding of Biotech Sector
  • 2.4.2 Technological Innovation
  • 2.4.3 Government Funding
  • 2.4.4 Pharmaceutical Development and Bioanalytical Services
  • 2.4.5 The War on Cancer
  • 2.4.6 Current Oncology Drug Development
• 2.5 Outlook for Tumor Markers
• 2.6 Focus on Proteomics
  • 2.6.1 Scientific Background
  • 2.6.2 The Relationship between Proteins and Diseases
  • 2.6.3 Limitations of Existing Diagnostic Approaches
  • 2.6.4 Addressing the Heterogeneity of Cancer
  • 2.6.5 Validation of Biomarkers Through Proper Study Design
  • 2.6.6 Exploiting the Power of Mass Spectrometry to Improve Assay Specificity
  • 2.6.7 Creating and Maintaining a Multi-Disease Product Pipeline
  • 2.6.8 Partnerships for Developing Proteomic Biomarkers
• 2.7 Epigenic Markers for Cancer
• 2.8 Molecular Diagnostics Testing for Cancer
• 2.9 Market Opportunities
  • 2.9.1 Industry Overview
  • 2.9.2 Medical Indications and Medically Useful Information
  • 2.9.3 Research Market
  • 2.9.4 Competition
  • 2.9.5 Diagnostic Services
  • 2.9.6 Clinical Image Analysis
  • 2.9.7 Research Imaging Market
  • 2.9.8 Genomic Disease Management and In Vitro Diagnostic Multivariate Index Assays (IVDMIA)
  • 2.9.9 Predictive Expression Profiles

3. Market Analysis of the Cancer Biomarkers Space

• 3.1 Scope of this Chapter
• 3.2 The Overall Market Opportunity and Segmentation of the Total Cancer Biomarkers Marketplace
• 3.3 Potential Cancer Biomarker Commercial Applications
  • 3.3.1 Market for Routine Tumor Markers
  • 3.3.2 Market for Genomic Cancer Biomarkers
  • 3.3.3 Market Size and Forecasts for Companion Diagnostic Tests for Cancer Therapeutics
  • 3.3.4 SWOT Analysis of the Major Cancer Biomarker Market Segments
    • 3.3.4.1 Traditional Serum Cancer Biomarkers
    • 3.3.4.2 Proteomic Cancer Biomarkers
    • 3.3.4.3 Companion Diagnostic Cancer Biomarkers
• 3.4 Cancer Biomarker Market Estimates by Tissue of Origin
  • 3.4.1 Colorectal
  • 3.4.2 Prostate
  • 3.4.3 Lung
  • 3.4.4 Breast
  • 3.4.5 Ovarian
• 3.5 Challenges Facing Cancer Biomarker Developers
• 3.6 Unmet Product Needs in the Cancer Biomarkers Space
• 3.7 Competitive Landscape of the Cancer Biomarkers Marketplace

4. Major Clinical Applications of Cancer Biomarkers

• 4.1 Launched Products and Pipeline
• 4.2 CYP2C9 Pharmacogenetics and Role in Personalized Medicine
• 4.3 Personalized Breast Cancer Therapy
• 4.4 Personalized NSCLC Therapy
• 4.5 AmpliChip®-based Personalized Medicine

5. Breast Cancer

• 5.1 Overview of Breast Cancer Disease
• 5.2 BRCA1 and BRCA2 Genes
  • 5.2.1 Types of Genetic Testing Available for Breast Cancer
    • 5.2.1.1 DNA Sequencing
    • 5.2.1.2 Multi-Site Analysis
    • 5.2.1.3 Single-Site Analysis
  • 5.2.2 BRCA Test Results
    • 5.2.2.1 What Does a Positive BRCA1 or BRCA2 Test Result Mean?
    • 5.2.2.2 What Does a Negative BRCA1 or BRCA2 Test Result Mean?
    • 5.2.2.3 What Does an Ambiguous BRCA1 or BRCA2 Test Result Mean?
    • 5.2.2.4 What are the Options for a Person Who Tests Positive?
  • 5.2.3 What are Some of the Benefits of Genetic Testing for Breast Cancer Risk?
  • 5.2.4 What Are Some of the Risks of Genetic Testing for Breast and Ovarian Cancer Risk?
• 5.3 Estrogen Receptors and Breast Cancer
  • 5.3.1 Expression and Prognostic Value of ER
  • 5.3.2 Progesterone Receptors and Breast Cancer
  • 5.3.3 ER and PR Predict Response to Endocrine Therapy
• 5.4 HER2 Gene and Protein
  • 5.4.1 HER2 Tests
    • 5.4.1.1 IHC Test
    • 5.4.1.2 FISH Test
    • 5.4.1.3 Questions About Testing
    • 5.4.1.4 HER2 Tumor Status
• 5.5 Herceptin® Treatment
• 5.6 Tumor Assays for Adjuvant Chemotherapy
• 5.7 Use of Genomics to Understand Breast Cancer
• 5.8 Genetic Analysis Solution
  • 5.8.1 The Use of Proteomics in Breast Cancer
  • 5.8.2 Tissue Microarrays
  • 5.8.3 Protein Microarrays
• 5.9 Gene Expression Microarrays and Recurrence Prediction
  • 5.9.1 Oncotype DX
  • 5.9.2 Oncotype DX for Breast Cancer
  • 5.9.3 Risk Assessment
  • 5.9.4 Use of Chemotherapy
  • 5.9.5 Utility of the Oncotype Test
  • 5.9.6 Clinical Development and Validation of Oncotype DX
    • 5.9.6.1 Clinical Development of the Oncotype DX Recurrence Score
    • 5.9.6.2 Clinical Validation of Prediction of Recurrence and Survival in N-, ER+ Patients Treated with Tamoxifen
    • 5.9.6.3 Oncotype DX Predicts the Likelihood of Recurrence
    • 5.9.6.4 Oncotype DX Predicts the Likelihood of Breast Cancer Survival in a Community Hospital Setting
    • 5.9.6.5 Oncotype DX Predicts both Prognosis and Tamoxifen Benefit
• 5.10 Economic Benefits of Oncotype DX
• 5.11 Increased Clinical Utility of Oncotype DX
• 5.12 Second Generation Oncotype DX
  • 5.12.1 Recurrence and Benefit Test for N-, ER- Breast Cancer
  • 5.12.2 Taxane Benefit Test
• 5.13 MammaPrint
• 5.14 Rotterdam Signature 76-Panel
• 5.15 Summary of Microarray Technologies
• 5.16 Mass Spectrometry-based Approaches
  • 5.16.1 Gel-based Approaches
  • 5.16.2 Non-Gel-based Approaches
    • 5.16.2.1 SELDI-TOF MS
    • 5.16.2.2 SELDI and Prognosis
    • 5.16.2.3 SELDI and Treatment Monitoring
  • 5.16.3 Limitations of Mass Spectroscopy
• 5.17 Outlook
• 5.18 Future Perspectives
• 5.19 Breast Cancer Program (NMP66)
• 5.20 Myriad Genetics
• 5.21 Veridex GeneSearch™ Breast Lymph Node
• 5.22 OncoVue Cancer Risk Test
• 5.23 Research Biomarkers for Breast Cancer
• 5.24 Protein Biomarkers for Breast Cancer Prevention
• 5.25 Biomarker Prognosis of Breast Cancer Treated with Doxorubicin

6. Ovarian Cancer

• 6.1 Serum Markers
• 6.2 Biomarkers
  • 6.2.1 Strategies for Discovering New Cancer Biomarkers
• 6.3 Serum Protein Biomarkers for Ovarian Cancer
  • 6.3.1 Clinical Proteomics
• 6.4 Ovarian Cancer Triage Testing
  • 6.4.1 Vermillion' s Ovarian Cancer Triage Diagnostic Program

7. Prostate Cancer

• 7.1 Overview
  • 7.1.1 Prevalence
  • 7.1.2 Prostate Cancer Progression and Recurrence Test
  • 7.1.3 Current Market Size
• 7.2 Genes Involved in Prostate Cancer
• 7.3 Androgen Independence
• 7.4 Gene Markers in Prostate Cancer
• 7.5 Microarray Gene Identification of Prostate Biomarkers
• 7.6 GEArray DNA Microarrays
• 7.7 Vermillion' s Cancer Diagnostic Program
• 7.8 Hepsin
• 7.9 Matritech' s Prostate Cancer Program (NMP48)
• 7.10 Gen-Probe' s PCA3 Assay
• 7.11 Early Prostate Cancer Antigen-2 (EPCA-2)
• 7.12 Mass Spectrometry
• 7.13 Summary

8. Bladder Cancer

• 8.1 Overview
  • 8.1.1 Prevalence
  • 8.1.2 Progression and Recurrence
  • 8.1.3 Bladder Cancer Risk Factors
  • 8.1.4 Bladder Cancer Symptoms
• 8.2 Bladder Cancer Tests
• 8.3 UroVysion Bladder Cancer Kit
• 8.4 Ikoniscope® Robotic Digital Microscopy Platform
  • 8.4.1 The CellOptics Platform
  • 8.4.2 Cell Staining and Genetic Characterization
  • 8.4.3 Ikoniscope/IkoniLAN Automated Microscopy
• 8.5 Nuclear Matrix Protein Markers
• 8.6 ImmunoCyt™/uCyt+™
• 8.7 Cangen Microsatellite DNA
• 8.8 Bladder Cancer Market
  • 8.8.1 Urologist Market
  • 8.8.2 Clinical Lab Market
  • 8.8.3 Primary Care Market
  • 8.8.4 Private and Public Sector Markets
  • 8.8.5 POC Market
  • 8.8.6 Market Distribution
  • 8.8.7 Reimbursement

9. Colorectal Cancer

• 9.1 Overview
  • 9.1.1 Prevalence
  • 9.1.2 Progression and Recurrence
• 9.2 Screening for CRC
  • 9.2.1 Stool-based DNA (sDNA) Screening
• 9.3 Almac Diagnostics DSA
• 9.4 Colon Cancer Program (NMP35)
• 9.5 Myriad Genetics Colaris AP Risk Assessment
• 9.6 Summary

10. Genetic Diagnostics Set to Revolutionize Cancer Diagnostic Testing

• 10.1 Overview
  • 10.1.1 Clinicians Need for More Information with Regard to Therapeutic Treatment Drives Demand for Pharmacogenomic Testing
  • 10.1.2 Predictive Medicine Shows Potential for Genetic Diagnostics
  • 10.1.3 Different Rates of Growth
  • 10.1.4 Effective Competitive Strategies
  • 10.1.5 Improvements in Marketing Effectiveness
  • 10.1.6 Emerging Technologies Imply Start of a New Era and Offer Tremendous Growth Opportunities
  • 10.1.7 Increased Market Share
  • 10.1.8 Technologies Used in Genetic Testing
• 10.2 AMAS Test
• 10.3 Corixa Antibodies as Tumor Markers
• 10.4 Cytovision
• 10.5 Ariol System
• 10.6 Mammaglobin Protein Expression
• 10.7 L523S or KOC RNA Binding Protein
• 10.8 CA1-18 from EDP Biotech

11. Leukemia Biomarkers

• 11.1 Overview
  • 11.1.1 Prevalence
    • 11.1.1.1 Progression and Recurrence

12. Lung Cancer

13. Enabling Technologies for Oncology Biomarker Discovery

• 13.1 Automated Cellular Imaging System (ACIS®)
  • 13.1.1 ACIS for HER2 Protein Expression Testing
  • 13.1.2 ACIS for ER Protein Expression Testing
  • 13.1.3 ACIS for PR Protein Expression Testing
  • 13.1.4 ACIS for Cell Proliferation Expression
  • 13.1.5 ACIS for Protein Expression
  • 13.1.6 ACIS for Protein Micrometastases in Bone Marrow
  • 13.1.7 ACIS for Protein Micrometastases in Tissue
  • 13.1.8 ACIS for Tissue Microarray
  • 13.1.9 ACIS for DNA Ploidy
  • 13.1.10 ACIS for HPV
• 13.2 DNA Methylation
  • 13.2.1 Differential Methylation Hybridization (DMH)
  • 13.2.2 MIRA-Assisted Microarrays for DNA Methylation Analysis and Cancer Diagnosis
• 13.3 Proteomics
  • 13.3.1 Proteomics Technologies for Cancer Marker Discovery
  • 13.3.2 Validation of Candidate Biomarkers
  • 13.3.3 Requirements Bringing a New Marker into the Market
  • 13.3.4 Value Chain in the Development of New Cancer Biomarkers
• 13.4 Secreted Proteins as Cancer Biomarkers
  • 13.4.1 Markers of Known Tissue Origin
  • 13.4.2 Secreted Proteins as Low Abundance Markers
  • 13.4.3 Secreted Proteins in Tissue and Blood
• 13.5 Noncodings RNA as Potential Tumor Markers
  • 13.5.1 miRNA Meets Microarray
  • 13.5.2 Mimetics and Inhibitors
  • 13.5.3 Clinical Patterns in Cancer
• 13.6 Architect TIMP-1 (Tissue Inhibitor of Metalloproteinases-1) Immunoassay for Colorectal Cancer Detection
• 13.7 Companies Developing Automated Microscope-based Analysis Systems
• 13.8 Companies Developing Research Products for Tumor Cell Isolation
• 13.9 Companies Supplying Fluorescently Labeled Antibodies to Characterize Tumor Cells
• 13.10 PerkinElmer High Throughput Platforms: AlphaScreen®, AequoScreen®, DELFIA® and LANCE® Technologies

14. Biomarker Tests Co-developed with Cancer Therapeutics as Companion Diagnostics

• 14.1 Sector Overview
• 14.2 Companion Diagnostics
• 14.3 EGFR for Colorectal Cancer and Camptostar (Irinotecan)
• 14.4 EGFR Express and Erbitux (Cetuximab)
• 14.5 HER2 and Heceptin
• 14.6 Myriad' s TheraGuide 5-FU
• 14.7 TheraScreen: EGFR29
• 14.8 Drivers and Barriers to Companion Diagnostics
• 14.9 Partnerships with Pharma Companies to Identify Therapeutic Targets
• 14.10 Future Developments for Companion Diagnostics

15. Companion Diagnostics and Personalized Medicine: Biology, Approaches, Pipeline and Regulatory Trends

• 15.1 Scope of this Chapter
• 15.2 Introduction to Companion Diagnostics and Personalized Medicine
• 15.3 The Compelling Case for Personalized Medicine
• 15.4 Drug Metabolism and Implications for Companion Diagnostics and Personalized Medicine
• 15.5 Examples of Personalized Medicine
• 15.6 Personalized Medicine and Companion Diagnostics Testing Product Pipeline
• 15.7 The Personalized Medicine Coalition
• 15.8 Regulatory Trends and Guidelines in the Personalized Medicine Space
• 15.8.1 The Changing Regulatory Landscape for Personalized Medicine
• 15.9 Patenting Personalized Medicine
• 15.10 The Leading Edge of Personalized Medicine: Specific Examples of Clinical Situations Where Personalized Medicine and Companion Diagnostics is Appropriate and Being Deployed
  • 15.10.1 EGFR Assay
  • 15.10.2 Individualized Warfarin Therapy
  • 15.10.3 UGT1A1 Molecular Assay for Camptosar
  • 15.10.4 Response to Gleevec in Gastrointestinal Stromal Tumors
  • 15.10.5 LabCorp, ARCA Personalized Medicine Deal for Cardiovascular Diseases
  • 15.10.6 Osmetech Licenses Epidauros Biotechnologie AG CYP2D6 Biomarker to Push into Companion Diagnostics
• 15.11 Companion Diagnostics and Personalized Medicine: Qualitative and Quantitative Market Analysis
  • 15.11.1 Market Analysis of Molecular Diagnostics and Companion Diagnostics and Personalized Medicine
  • 15.11.2 Diagnostics vs. Pharmaceuticals
  • 15.11.3 Molecular Diagnostic Market
  • 15.11.4 Molecular Diagnostics Technology Platforms and their Impact on Personalized Medicine
• 15.12 Snapshot of Companion Diagnostics Industry Structure
• 15.13 The Case for Theranostics (Therapeutic/Companion Diagnostic)
• 15.14 Personalized Medicine Market Analysis-Market Survey Data Characterizing the Qualitative and Quantitative Industry Parameters
• 15.15 How the Market Segregates Today
• 15.16 Timeline for Impact of Various Segments in Personalized Medicine
• 15.17 Challenges for Personalized Therapeutics and Companion Diagnostics Development
• 15.18 Macro Trends in Personalized Medicine
• 15.19 Personalized Medicine and Companion Diagnostics: Industry SWOT Analysis

16. Cancer Biomarker Testing Sector and Company Analysis

• 16.1 Abbott Molecular, Inc. (Formerly Vysis, Inc.)
• 16.2 Agendia
• 16.3 AMDL, Inc.
• 16.4 Aureon Laboratories, Inc.
• 16.5 BioCurex
• 16.6 Biomarker Technologies
• 16.7 Biomedical Diagnostics LLC
• 16.8 Biomerica
• 16.9 Biomira, Inc.
• 16.10 Biomoda
• 16.11 Byk Gulden
• 16.12 Clarient
• 16.13 Correlogic Systems, Inc.
• 16.14 Cytogen Corporation
• 16.15 Dako (Formerly Dako Cytomation)
• 16.16 diaDexus
• 16.17 Diagnocure, Inc. (ImmunoCyt™/uCyt+™)
• 16.18 DxS Ltd.
• 16.19 Epigenomics
• 16.20 Exagen Diagnostics, Inc.
• 16.21 Genesis Genomics
• 16.22 Health Discovery Corporation
• 16.23 Immunicon
• 16.24 Ipsogen
• 16.25 InterGenetics
• 16.26 Miraculins, Inc.
• 16.27 Molecular Devices Inc. (Formerly Arcturus Bioscience, Inc.)
• 16.28 Myriad Genetics, Inc.
• 16.29 Orion Genomics
• 16.30 Power3 Medical Products
• 16.31 Qiagen N.V.
• 16.32 SuperArray Bioscience Corporation
• 16.33 Upstream Biosciences, Inc.
• 16.34 Ventana Medical Systems, Inc.
• 16.35 Veridex
• 16.36 Vermillion

17. Business Trends in the Industry

• 17.1 Industry Consolidation
• 17.2 Breadth of Product Offering and Pricing
• 17.3 Government Regulation of Medical Devices
  • 17.3.1 FDA Guidance on Drug Test Co-development
• 17.4 Strategic Business and Marketing Considerations
• 17.5 Commercial Opportunities in Cancer Markers
  • 17.5.1 Licensing and Intellectual Property (IP) Constraints and how they will Impact New Product Development
• 17.6 Moderators of Growth
  • 17.6.1 Roadblocks to Integrating Cancer Biomarkers into Clinical Practice
• 17.7 Biotechnology Industry Trends
• 17.8 Pharmaceutical Industry Trends
• 17.9 Acquisition, License Agreement, Partnerships
• 17.10 Legal Developments
• 17.11 Sales and Marketing Strategies for Tumor Marker Tests
  • 17.11.1 North American Market
  • 17.11.2 International Markets
    • 17.11.2.1 Europe
    • 17.11.2.2 Central and South America
    • 17.11.2.3 Asia/Pacific
• 17.12 Product Commercialization
• 17.13 Reimbursement
• 17.14 Self Referral Rules
• 17.15 Health Insurance Portability and Accountability Act
• 17.16 Clinical Laboratory Improvement Amendments (CLIA)
• 17.17 In-Vitro Diagnostic Directive (IVDD) and Medical Device Regulations
• 17.18 FDA' s Quality System Regulation (QSR)
• 17.19 FDA' s OIVD on IVDMIAs
• 17.20 FDA' s Qualification of Cancer Biomarkers
  • 17.20.1 Regulatory Perspectives of Biomarker Validation
• 17.21 Genetic Tests and Medical Records
  • 17.21.1 Laws against Genetic Discrimination
• 17.22 Medicare Reimbursement
  • 17.22.1 Medicare Part B Spending Trends
• 17.23 Global Drivers of Clinical Laboratory Testing
• 17.24 Global Outlook for Cancer Biomarkers
  • 17.24.1 Which Companies are Utilizing Cutting-Edge Technologies to Develop, Validate and Implement Cancer Biomarkers for Clinical Use?
  • 17.24.2 What Impediments Still Exist to Incorporating Promising Research into Clinical Practice?
  • 17.24.3 Which Biomarkers Show the Most Promise for Approval?
  • 17.24.4 How can Regulatory Oversight Drive Approval and Adoption of New Technologies?
  • 17.24.5 Which Alliances Show the Greatest Synergy in Bringing Valid Biomarkers to Market?
  • 17.24.6 Which Shared Technologies are Driving the Most Encouraging Development?
  • 17.24.7 How Strategic Alliances and Interdisciplinary Involvement Drive Development and Implementation of Emerging Biomarker Technologies
• 17.25 Oncology Biomarker Qualification Initiative
• 17.26 FDA Critical Path
• 17.27 FDA Criteria for a Valid Biomarker

18. Companies Entering the Cancer Diagnostics Market with Novel Technology Platforms

• 18.1 Abbott Diagnostics
• 18.2 Affymetrix, Inc.
• 18.3 Agendia BV
• 18.4 Agensys, Inc.
• 18.5 Almac Group
• 18.6 AMDL, Inc.
• 18.7 Aureon Laboratories, Inc.
• 18.8 Bayer Diagnostics Corporation
• 18.9 Beckman Coulter, Inc.
• 18.10 Biocode S.A.
• 18.11 BioCurex, Inc.
• 18.12 Biomarker Technologies LLC
• 18.13 Biomedical Diagnostics LLC
• 18.14 Biomerica
• 18.15 bioMérieux
• 18.16 Biomira, Inc.
• 18.17 Biomoda, Inc.
• 18.18 Bruker Daltonics, Inc.
• 18.19 Byk Gulden
• 18.20 Cangen Biotechnologies, Inc.
• 18.21 Caprion Proteomics
• 18.22 Celera Diagnostics
• 18.23 Cepheid
• 18.24 Clarient, Inc.
• 18.25 Claros Diagnostics, Inc.
• 18.26 Clinical Data, Inc.: PGxHealth and Cogenics
• 18.27 Correlogic Systems, Inc.
• 18.28 CytoCore (Formerly Molecular Diagnostics, Inc.)
• 18.29 Cytogen Corporation
• 18.30 Dako (Formerly Dako Cytomation)
• 18.31 diaDexus LLC
• 18.32 DiagnoCure, Inc.
• 18.33 Diagnostic Products Corporation
• 18.34 Diagnostic Systems Laboratories, Inc.
• 18.35 Digene Corporation
• 18.36 DRG International, Inc.
• 18.37 DxS Ltd.
• 18.38 EDP Biotech Corporation
• 18.39 Eisai Co., Ltd.
• 18.40 Epigenomics
• 18.41 Exact Sciences Corporation
• 18.42 Exagen Diagnostics, Inc.
• 18.43 Gene Logic, Inc.
• 18.44 Genesis Genomics, Inc.
• 18.45 Genomic Health, Inc.
• 18.46 Gen-Probe, Inc.
• 18.47 Health Discovery Corporation
• 18.48 Hologic, Inc. (Formerly Cytyc Corporation)
• 18.49 Ikonisys, Inc.
• 18.50 Immunicon Corporation
• 18.51 Immunomedics, Inc.
• 18.52 Incyte Pharmaceuticals, Inc.
• 18.53 InterGenetics®
• 18.54 Ipsogen
• 18.55 LabCorp®
• 18.56 Matritech, Inc.
• 18.57 Miraculins, Inc.
• 18.58 Mitsubishi Kagaku Medical
• 18.59 Molecular Devices (Formerly Arcturus Biosciences, Inc.)
• 18.60 Myriad Genetics, Inc.
• 18.61 NimbleGen Systems, Inc.
• 18.62 Northwest Biotherapeutics, Inc.
• 18.63 Oncotech, Inc.
• 18.64 Orion Genomics
• 18.65 Oxford Genome Sciences
• 18.66 Panacea Pharmaceuticals, Inc.
• 18.67 Phenomenone Discoveries
• 18.68 Polymedco, Inc.
• 18.69 Power3 Medical Products
• 18.70 Proteome Systems Ltd.
• 18.71 Qiagen N.V.
• 18.72 Sanko Junyaku Co., Ltd.
• 18.73 SensiGen LLC
• 18.74 SuperArray Bioscience Corporation
• 18.75 Third Wave Technologies, Inc.
• 18.76 Tosoh Medics, Inc.
• 18.77 TriPath Imaging, Inc.
• 18.78 Upstream Biosciences, Inc.
• 18.79 Ventana Medical Systems, Inc.
• 18.80 Veridex LLC
• 18.81 Vermillion, Inc. (Formerly Ciphergen)

Appendix 1: Cancer Biomarker Centers of Research

Appendix 2: Myriad Patents on Genes BRAC1 and BRAC2

Appendix 3: Common Laboratory Tests for Cancer

Appendix 4: Questions/Issues in the Cancer Biomarkers Space

Appendix 5: Cancer Markers Currently in Common Clinical Use

Appendix 6: International Federation of Gynecology and Obstetrics (FIGO) Staging System for Primary Carcinoma of the Ovary

Appendix 7: FDA Guidance for Industry: Pharmacogenomic Data Submission

• A7.1 Introduction
• A7.2 Background
• A7.3 Submission Policy
  • A7.3.1 General Principles
  • A7.3.2 Specific Uses of Pharmacogenomic Data in Drug Development and Labeling
  • A7.3.3 Benefits of Voluntary Submissions to Sponsors and FDA
• A7.4 Submission of Pharmacogenomic Data
  • A7.4.1 Submission of Pharmacogenomic Data During the IND Phase
  • A7.4.2 Submission of Pharmacogenomic Data to a New NDA, BLA, or Supplement
  • A7.4.3 Submission to a Previously Approved NDA or BLA
  • A7.4.4 Compliance with 21 CFR Part 58
  • A7.4.5 Submission of Voluntary Genomic Data from Application-Independent Research
• A7.5 Format and Content of a VGDS
• A7.6 Process for Submitting Pharmacogenomic Data
• A7.7 Agency Review of VGDSs

Glossary

INDEX OF FIGURES

• Figure 3.1: Potential Market for Cancer Biomarkers, 2006
• Figure 3.2: Segmentation of the Cancer biomarkers Marketplace Based Upon Commercial Offerings-Products and Services
• Figure 3.3: Geographical Distribution of Cancer Tumor Diagnostic Testing
• Figure 3.4: Cancer Biomarkers Research Market, 2006-2011
• Figure 3.5: Breast Cancer Biomarker Market Potential, 2005
• Figure 3.6: Challenges in the Study or Utilization of Proteomic Cancer Biomarkers
• Figure 3.7: Challenges in the Study or Utilization of Companion Diagnostic Cancer Biomarkers
• Figure 3.8: Challenges in the Study or Utilization of Serum Cancer Markers
• Figure 3.9: Top Unmet Needs in Commercial Products in the Cancer Biomarkers Space
• Figure 5.1: Hybridization Process
• Figure 5.2: FISH Test Procedure
• Figure 5.3: Gene Expression Profiling
• Figure 15.1: Phase I and II Processes of Drug Metabolism
• Figure 15.2: Human Phase I Enzymes
• Figure 15.3: Human Phase II Enzymes
• Figure 15.4: Hepatic Distribution of Human CYP450
• Figure 15.5: Relative Contribution of CYP450 Enzymes to Drug Metabolism
• Figure 15.6: Genetic Components Determine Drug Metabolism
• Figure 15.7: From Genetic Content to Personalized Medicine
• Figure 15.8: Remuneration for Diagnostics
• Figure 15.9: Breakout of the Molecular Diagnostics Marketplace
• Figure 15.10: Molecular Diagnostics Market Segmentation
• Figure 15.11: Molecular Diagnostics Market Segmentation by Technology
• Figure 15.12: Market Survey Respondent Demographics
• Figure 15.13: Breakout of the Respondent Pool by Affiliation
• Figure 15.14: Segmentation of the Personalized Medicine Market
• Figure 15.15: Personalized Medicine Market Drivers
• Figure 15.16: Challenges in the Personalized Medicine Space
• Figure 16.1: Epigenomics Product Development Pipeline
• Figure 17.1: Medicare Part B Spending on Clinical Laboratory Services, 1991-2005

INDEX OF TABLES

• Table 2.1: Cancer Biomarkers at the Nexus Point
• Table 2.2: Drug Development by Type of Cancer
• Table 2.3: Organ Specific Medicines in Development for Cancer, 2006
• Table 2.4: Estimates for the Leading Sites of New Cancer Cases and Deaths in the U.S. by Sex, 2007
• Table 2.5: Estimated Worldwide Number of New Cancer Cases and Deaths by Type of Cancer
• Table 2.6: Estimated Number of New Cancer Cases and Deaths by Region
• Table 2.7: Cancer Death Rates per 100,000 Population (and Rank) for All Cancer Sites by Country
• Table 2.8: Cancer Associated Genes
• Table 2.9: Carcinogens in the Workplace
• Table 2.10: Cancer Biomarker Markets
• Table 2.11: Private Funding Levels for the Biotechnology Segment, 1995-2006
• Table 2.12: Global Pharmaceutical Industry R&D Spending, 1995-2006
• Table 2.13: U.S. Government NIH Research Budget, 1995-2007
• Table 2.14: Tumor Markers Currently in Common Use
• Table 2.15: Herceptin Worldwide Sales, 1999-2007
• Table 2.16: Classes of Drugs Used to Treat Breast Cancer
• Table 2.17: Solutions to Biomarker Developments
• Table 2.18: Vermillion Collaborations
• Table 2.19: Uses of Molecular Diagnostics in Detection and Management of Cancer
• Table 2.20: U.S. Cancer Diagnostic Testing Market Size, 2005-2012
• Table 2.21: Market Opportunities for Cancer Biomarker Technology Platforms
• Table 3.1: Characteristics of Different Cancer Biomarker Types and Associated Market Opportunities
• Table 3.2: Segmentation of the Cancer Biomarker Market by Type/Lineage of Cancer Biomarkers and Market Size
• Table 3.3: In Vitro Cancer Marker Market Segments Worldwide, 2001 and 2007
• Table 3.4: Worldwide Market Size in Dollar Volume for Tumor Marker Assays Product Market, 2001-2010
• Table 3.5: U.S. Market Size in Dollar Volume for Tumor Marker Assays Product Market, 2001-2010
• Table 3.6: Worldwide In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010
• Table 3.7: U.S. In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010
• Table 3.8: Japanese In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010
• Table 3.9: European In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010
• Table 3.10: Global Distribution of IVD Cancer Tumor Marker Diagnostic Testing, 2005
• Table 3.11: Estimated Market Share of Major Competitors in U.S. Cancer Tumor Marker Diagnostics Market
• Table 3.12: Major Presence in Cancer Tumor Marker Diagnostics Markets
• Table 3.13: Worldwide CEA Sales, 2001-2010
• Table 3.14: U.S. CEA Sales, 2001-2010
• Table 3.15: Cancer Genomic Biomarker Markets, 2002-2012
• Table 3.16: Cancer Biomarkers Research Market Forecast, 2006-2011
• Table 3.17: Cancer Biomarker Market Estimates by Tissue of Origin
• Table 3.18: Companies Developing New Proteomic Cancer Biomarker Technology Platforms
• Table 4.1: Cancer Biomarkers Used to Maximize Likelihood of Response
• Table 4.2: Biomarkers for Monitoring Therapeutic Effectiveness and Resistance
• Table 4.3: Biomarkers for Dose Response of Therapy
• Table 4.4: Decision on Optimal Duration of Therapy
• Table 5.1: U.S. Breast Cancer Rate Decline, 2002-2006
• Table 5.2: BRCA Development Model
• Table 5.3: BRCA Test Development and Commercialization
• Table 5.4: BRAC Analysis
• Table 5.5: Revenue for BRACAnalysis® Risk Assessment Test, 2002-2006
• Table 5.6: GEArray DNA Microarrays and RT2 Profiler PCR Arrays
• Table 5.7: Product Development Opportunities in Breast Cancer
• Table 5.8: Concentration of Some Abundant Proteins, New Cancer Biomarkers Identified by SELDI-TOF, and Classical Cancer Biomarkers in Serum
• Table 5.9: Questions Related to Diagnostic SELDI-TOF Technology
• Table 6.1: Worldwide CA-125 Sales, 2001-2010
• Table 6.2: U.S. CA-125 Sales, 2001-2010
• Table 6.3: Some Clinically Established Cancer Serum Markers Currently in Use for Cancer
• Table 6.4: Pathophysiology of Ovarian Cancer and Characterization of Ovarian Epithelial Tumors
• Table 7.1: Worldwide PSA Sales, 2000-2010
• Table 7.2: U.S. PSA Sales, 2000-2010
• Table 7.3: Molecular Gene Markers for Prostate Cancer
• Table 8.1: Worldwide Bladder Cancer Marker Sales, 2001-2010
• Table 8.2: U.S. Bladder Cancer Marker Sales, 2001-2010
• Table 8.3: Worldwide NMP22 Sales, 2001-2010
• Table 8.4: Summary of Matritech' s Product Development Programs
• Table 8.5: Opportunities for Bladder Cancer Biomarkers
• Table 9.1: TNM Staging for Colorectal Cancer
• Table 10.1: Genetic Diagnostics Market, 2004-2012
• Table 13.1: Genomic and Proteomic Technologies
• Table 14.1: Potential Benefits of Biomarkers as Companion Diagnostics
• Table 14.2: Utility of Biomarker as Companion Diagnostics to Drug Development
• Table 14.3: Device Submission Elements for the FDA
• Table 14.4: Summary of Biomarker Use in the Commercialization of Novel Oncology Pharmacotherapeutics
• Table 14.5: Pharmacoeconomic Challenges to the Implementation of Biomarkers as Companion Diagnostic Tests
• Table 15.1: Percentage of Non-Responders in Various Drug Classes
• Table 15.2: High Profile Drug Withdrawals from the Marketplace
• Table 15.3: Drug Metabolism Drives Drug Efficacy/Toxicity
• Table 15.4: Population Frequency of the Various Cytochromes
• Table 15.5: Selected List of Personalized Medicine Tests
• Table 15.6: Personalized Medicine and Companion Diagnostics Product Pipeline
• Table 15.7: Marketed Personalized Therapies, 2006
• Table 15.8: Various Molecular Diagnostics Technologies: Timeline for Impact
• Table 15.9: Various Molecular Diagnostics Technologies: Impact on Different Therapeutic Areas in Personalized Medicine
• Table 15.10: Various Molecular Diagnostics Technologies: Technical Challenges in the Deployment for Personalized Medicine
• Table 15.11: Classification of Diagnostics by Risk
• Table 15.12: Areas in Personalized Medicine-Timeline of Impact
• Table 15.13: Impact of Personalized Medicine on Various Therapeutic Areas
• Table 15.14: Hurdles in Personalized Medicine and Companion Diagnostics Development in Various Therapeutic Areas
• Table 15.15: Market Opportunities in Personalized Medicine
• Table 15.16: Challenges for Market Adoption of the Various Personalized Medicine Tests
• Table 15.17: Personalized Medicine Industry SWOT
• Table 16.2: Clarient Revenue, 2002-2006
• Table 16.3: Clarient Percentage of Revenue, 2004-2006
• Table 16.4: Opportunities for Biomarkers in Cancer Diagnosis and Treatment
• Table 16.5: Myriad Biomarker Revenue, 2002-2006
• Table 17.1: List and Discounted Prices for Abbott Tumor Marker Tests
• Table 17.2: Hospital Laboratory Share of Part B Medicare Spending, 1996-2005
• Table 17.3: Medicare Spending on Clinical Lab Services, 1991-2005
• Table 17.4: Medicare Part B Spending Per Medicare Enrollee, 1998-2005
• Table 18.1: Tumor Diagnosis Immunoassay
• Table 18.2: Tumor Diagnosis Radioimmunoassay
• Table 18.3: Summary of Matritech' s Product Development Programs
• Table A1: Team Descriptions
• Table A5: Cancer Markers in Use