Biomarker Technology Platforms for Cancer Diagnoses and Therapies

Table of Contents:

1. Overview 12
1.1 Statement of Report 12
1.2 About This Report 12
1.3 Scope of the Report 12
1.4 Objectives 13
1.5 Methodology 14
1.6 Executive Summary 15
2. Introduction to Cancer Biology and the Diagnostic Industry 17
2.1 Biomarkers 17
2.1.1 The Biomarker Market Drivers 17
2.1.1.1 The Sector 17
2.1.1.2 The Critical Path Opportunities 17
2.1.1.3 The Capital Markets 17
2.2 Cancer Detection and Treatment with Biomarkers 18
2.2.1 The Problem 19
2.3 Cancer: The Disease 21
2.3.1 Metastasis 21
2.3.2 Demographics and Statistics of Cancer 22
2.4 Drivers of the Biotech and Diagnostics Industry 28
2.4.1 Venture Funding of Biotech Sector 29
2.4.2 Technological Innovation 30
2.4.3 Government Funding 30
2.4.4 Pharmaceutical Development and Bioanalytical Services 30
2.4.5 The War on Cancer 32
2.4.6 Current Oncology Drug Development 32
2.5 Outlook for Tumor Markers 32
2.6 Focus on Proteomics 35
2.6.1 Scientific Background 35
2.6.2 The Relationship between Proteins and Diseases 35
2.6.3 Limitations of Existing Diagnostic Approaches 36
2.6.4 Addressing the Heterogeneity of Cancer 36
2.6.5 Validation of Biomarkers through Proper Study Design 37
2.6.6 Exploiting the Power of Mass Spectrometry to Improve Assay Specificity 37
2.6.7 Creating and Maintaining a Multi-Disease Product Pipeline 39
2.6.8 Partnerships for Developing Proteomic Biomarkers 39
2.7 Epigenic Markers for Cancer 40
2.8 Molecular Diagnostics Testing for Cancer 41
2.9 Market Opportunities 41
2.9.1 Industry Overview 42
2.9.2 Medical Indications and Medically Useful Information 44
2.9.3 Research Market 45
2.9.4 Competition 46
2.9.5 Diagnostic Services 46
2.9.6 Clinical Image Analysis 46
2.9.7 Research Imaging Market 46
2.9.8 Genomic Disease Management and In Vitro Diagnostic Multivariate Index Assays (IVDMIA) 47
2.9.9 Predictive Expression Profiles 48
3. Market Analysis of the Cancer Biomarkers Space 49
3.1 Scope of this Chapter 49
3.2 The Overall Market Opportunity and Segmentation of the Total Cancer Biomarkers Marketplace 49
3.3 Potential Cancer Biomarker Commercial Applications 52
3.3.1 Market for Routine Tumor Markers 53
3.3.2 Market for Genomic Cancer Biomarkers 58
3.3.3 Market Size and Forecasts for Companion Diagnostic Tests for Cancer Therapeutics 60
3.3.4 SWOT Analysis of the Major Cancer Biomarker Market Segments 62
3.3.4.1 Traditional Serum Cancer Biomarkers 62
3.3.4.2 Proteomic Cancer Biomarkers 63
3.3.4.3 Companion Diagnostic Cancer Biomarkers 64
3.4 Cancer Biomarker Market Estimates by Tissue of Origin 65
3.4.1 Colorectal 65
3.4.2 Prostate 66
3.4.3 Lung 66
3.4.4 Breast 66
3.4.5 Ovarian 67
3.5 Challenges Facing Cancer Biomarker Developers 67
3.6 Unmet Product Needs in the Cancer Biomarkers Space 69
3.7 Competitive Landscape of the Cancer Biomarkers Marketplace 71
4. Major Clinical Applications of Cancer Biomarkers 74
4.1 Launched Products and Pipeline 74
4.2 CYP2C9 Pharmacogenetics and Role in Personalized Medicine 76
4.3 Personalized Breast Cancer Therapy 76
4.4 Personalized NSCLC Therapy 77
4.5 AmpliChip®-based Personalized Medicine 77
5. Breast Cancer 78
5.1 Overview of Breast Cancer Disease 78
5.2 BRCA1 and BRCA2 Genes 79
5.2.1 Types of Genetic Testing Available for Breast Cancer 81
5.2.1.1 DNA Sequencing 81
5.2.1.2 Multi-Site Analysis 82
5.2.1.3 Single-Site Analysis 82
5.2.2 BRCA Test Results 82
5.2.2.1 What Does a Positive BRCA1 or BRCA2 Test Result Mean? 82
5.2.2.2 What Does a Negative BRCA1 or BRCA2 Test Result Mean? 82
5.2.2.3 What Does an Ambiguous BRCA1 or BRCA2 Test Result Mean? 83
5.2.2.4 What are the Options for a Person Who Tests Positive? 83
5.2.3 What are Some of the Benefits of Genetic Testing for Breast Cancer Risk? 84
5.2.4 What Are Some of the Risks of Genetic Testing for Breast and Ovarian Cancer Risk? 84
5.3 Estrogen Receptors and Breast Cancer 84
5.3.1 Expression and Prognostic Value of ER 84
5.3.2 Progesterone Receptors and Breast Cancer 85
5.3.3 ER and PR Predict Response to Endocrine Therapy 85
5.4 HER2 Gene and Protein 86
5.4.1 HER2 Tests 86
5.4.1.1 IHC Test 86
5.4.1.2 FISH Test 87
5.4.1.3 Questions About Testing 89
5.4.1.4 HER2 Tumor Status 90
5.5 Herceptin® Treatment 90
5.6 Tumor Assays for Adjuvant Chemotherapy 92
5.7 Use of Genomics to Understand Breast Cancer 93
5.8 Genetic Analysis Solution 94
5.8.1 The Use of Proteomics in Breast Cancer 95
5.8.2 Tissue Microarrays 96
5.8.3 Protein Microarrays 98
5.9 Gene Expression Microarrays and Recurrence Prediction 99
5.9.1 Oncotype DX 100
5.9.2 Oncotype DX for Breast Cancer 101
5.9.3 Risk Assessment 101
5.9.4 Use of Chemotherapy 101
5.9.5 Utility of the Oncotype Test 101
5.9.6 Clinical Development and Validation of Oncotype DX 102
5.9.6.1 Clinical Development of the Oncotype DX Recurrence Score 102
5.9.6.2 Clinical Validation of Prediction of Recurrence and Survival in N-, ER+ Patients Treated with Tamoxifen 102
5.9.6.3 Oncotype DX Predicts the Likelihood of Recurrence 103
5.9.6.4 Oncotype DX Predicts the Likelihood of Breast Cancer Survival in a Community Hospital Setting 103
5.9.6.5 Oncotype DX Predicts both Prognosis and Tamoxifen Benefit 104
5.10 Economic Benefits of Oncotype DX 104
5.11 Increased Clinical Utility of Oncotype DX 105
5.12 Second Generation Oncotype DX 106
5.12.1 Recurrence and Benefit Test for N-, ER- Breast Cancer 106
5.12.2 Taxane Benefit Test 106
5.13 MammaPrint 106
5.14 Rotterdam Signature 76-Panel 107
5.15 Summary of Microarray Technologies 107
5.16 Mass Spectrometry-based Approaches 108
5.16.1 Gel-based Approaches 108
5.16.2 Non-Gel-based Approaches 109
5.16.2.1 SELDI-TOF MS 109
5.16.2.2 SELDI and Prognosis 110
5.16.2.3 SELDI and Treatment Monitoring 111
5.16.3 Limitations of Mass Spectroscopy 111
5.17 Outlook 112
5.18 Future Perspectives 114
5.19 Breast Cancer Program (NMP66) 115
5.20 Myriad Genetics 115
5.21 Veridex GeneSearch™ Breast Lymph Node 116
5.22 OncoVue Cancer Risk Test 116
5.23 Research Biomarkers for Breast Cancer 116
5.24 Protein Biomarkers for Breast Cancer Prevention 117
5.25 Biomarker Prognosis of Breast Cancer Treated with Doxorubicin 117
6. Ovarian Cancer 118
6.1 Serum Markers 120
6.2 Biomarkers 121
6.2.1 Strategies for Discovering New Cancer Biomarkers 122
6.3 Serum Protein Biomarkers for Ovarian Cancer 122
6.3.1 Clinical Proteomics 123
6.4 Ovarian Cancer Triage Testing 124
6.4.1 Vermillion's Ovarian Cancer Triage Diagnostic Program 125
7. Prostate Cancer 127
7.1 Overview 127
7.1.1 Prevalence 127
7.1.2 Prostate Cancer Progression and Recurrence Test 127
7.1.3 Current Market Size 127
7.2 Genes Involved in Prostate Cancer 128
7.3 Androgen Independence 129
7.4 Gene Markers in Prostate Cancer 130
7.5 Microarray Gene Identification of Prostate Biomarkers 130
7.6 GEArray DNA Microarrays 132
7.7 Vermillion's Cancer Diagnostic Program 133
7.8 Hepsin 133
7.9 Matritech's Prostate Cancer Program (NMP48) 133
7.10 Gen-Probe's PCA3 Assay 134
7.11 Early Prostate Cancer Antigen-2 (EPCA-2) 134
7.12 Mass Spectrometry 135
7.13 Summary 137
8. Bladder Cancer 138
8.1 Overview 138
8.1.1 Prevalence 138
8.1.2 Progression and Recurrence 138
8.1.3 Bladder Cancer Risk Factors 138
8.1.4 Bladder Cancer Symptoms 138
8.2 Bladder Cancer Tests 138
8.3 UroVysion Bladder Cancer Kit 139
8.4 Ikoniscope® Robotic Digital Microscopy Platform 140
8.4.1 The CellOptics Platform 140
8.4.2 Cell Staining and Genetic Characterization 140
8.4.3 Ikoniscope/IkoniLAN Automated Microscopy 140
8.5 Nuclear Matrix Protein Markers 141
8.6 ImmunoCyt™/uCyt+™ 143
8.7 Cangen Microsatellite DNA 145
8.8 Bladder Cancer Market 145
8.8.1 Urologist Market 145
8.8.2 Clinical Lab Market 145
8.8.3 Primary Care Market 145
8.8.4 Private and Public Sector Markets 146
8.8.5 POC Market 146
8.8.6 Market Distribution 146
8.8.7 Reimbursement 146
9. Colorectal Cancer 147
9.1 Overview 147
9.1.1 Prevalence 147
9.1.2 Progression and Recurrence 147
9.2 Screening for CRC 149
9.2.1 Stool-based DNA (sDNA) Screening 150
9.3 Almac Diagnostics DSA 151
9.4 Colon Cancer Program (NMP35) 152
9.5 Myriad Genetics Colaris AP Risk Assessment 152
9.6 Summary 153
10. Genetic Diagnostics Set to Revolutionize Cancer Diagnostic Testing 154
10.1 Overview 154
10.1.1 Clinicians Need for More Information with Regard to Therapeutic Treatment Drives Demand for Pharmacogenomic Testing 154
10.1.2 Predictive Medicine Shows Potential for Genetic Diagnostics 154
10.1.3 Different Rates of Growth 155
10.1.4 Effective Competitive Strategies 155
10.1.5 Improvements in Marketing Effectiveness 155
10.1.6 Emerging Technologies Imply Start of a New Era and Offer Tremendous Growth Opportunities 155
10.1.7 Increased Market Share 155
10.1.8 Technologies Used in Genetic Testing 155
10.2 AMAS Test 156
10.3 Corixa Antibodies as Tumor Markers 156
10.4 Cytovision 157
10.5 Ariol System 157
10.6 Mammaglobin Protein Expression 157
10.7 L523S or KOC RNA Binding Protein 157
10.8 CA1-18 from EDP Biotech 158
11. Leukemia Biomarkers 159
11.1 Overview 159
11.1.1 Prevalence 159
11.1.1.1 Progression and Recurrence 159
12. Lung Cancer 160
13. Enabling Technologies for Oncology Biomarker Discovery 161
13.1 Automated Cellular Imaging System (ACIS®) 161
13.1.1 ACIS for HER2 Protein Expression Testing 162
13.1.2 ACIS for ER Protein Expression Testing 162
13.1.3 ACIS for PR Protein Expression Testing 162
13.1.4 ACIS for Cell Proliferation Expression 163
13.1.5 ACIS for Protein Expression 163
13.1.6 ACIS for Protein Micrometastases in Bone Marrow 163
13.1.7 ACIS for Protein Micrometastases in Tissue 163
13.1.8 ACIS for Tissue Microarray 163
13.1.9 ACIS for DNA Ploidy 163
13.1.10 ACIS for HPV 163
13.2 DNA Methylation 164
13.2.1 Differential Methylation Hybridization (DMH) 164
13.2.2 MIRA-Assisted Microarrays for DNA Methylation Analysis and Cancer Diagnosis 164
13.3 Proteomics 165
13.3.1 Proteomics Technologies for Cancer Marker Discovery 165
13.3.2 Validation of Candidate Biomarkers 166
13.3.3 Requirements Bringing a New Marker into the Market 166
13.3.4 Value Chain in the Development of New Cancer Biomarkers 167
13.4 Secreted Proteins as Cancer Biomarkers 167
13.4.1 Markers of Known Tissue Origin 167
13.4.2 Secreted Proteins as Low Abundance Markers 167
13.4.3 Secreted Proteins in Tissue and Blood 167
13.5 Noncodings RNA as Potential Tumor Markers 167
13.5.1 miRNA Meets Microarray 168
13.5.2 Mimetics and Inhibitors 168
13.5.3 Clinical Patterns in Cancer 168
13.6 Architect TIMP-1 (Tissue Inhibitor of Metalloproteinases-1) Immunoassay for Colorectal Cancer Detection 168
13.7 Companies Developing Automated Microscope-based Analysis Systems 168
13.8 Companies Developing Research Products for Tumor Cell Isolation 169
13.9 Companies Supplying Fluorescently Labeled Antibodies to Characterize Tumor Cells 169
13.10 PerkinElmer High Throughput Platforms: AlphaScreen®, AequoScreen®, DELFIA® and LANCE® Technologies 169
14. Biomarker Tests Co-developed with Cancer Therapeutics as Companion Diagnostics 169
14.1 Sector Overview 170
14.2 Companion Diagnostics 171
14.3 EGFR for Colorectal Cancer and Camptostar (Irinotecan) 172
14.4 EGFR Express and Erbitux (Cetuximab) 172
14.5 HER2 and Heceptin 173
14.6 Myriad's TheraGuide 5-FU 173
14.7 TheraScreen: EGFR29 173
14.8 Drivers and Barriers to Companion Diagnostics 174
14.9 Partnerships with Pharma Companies to Identify Therapeutic Targets 175
14.10 Future Developments for Companion Diagnostics 175
15. Companion Diagnostics and Personalized Medicine: Biology, Approaches, Pipeline and Regulatory Trends 177
15.1 Scope of this Chapter 177
15.2 Introduction to Companion Diagnostics and Personalized Medicine 177
15.3 The Compelling Case for Personalized Medicine 179
15.4 Drug Metabolism and Implications for Companion Diagnostics and Personalized Medicine 180
15.5 Examples of Personalized Medicine 184
15.6 Personalized Medicine and Companion Diagnostics Testing Product Pipeline 186
15.7 The Personalized Medicine Coalition 188
15.8 Regulatory Trends and Guidelines in the Personalized Medicine Space 190
15.8.1 The Changing Regulatory Landscape for Personalized Medicine 192
15.9 Patenting Personalized Medicine 193
15.10 The Leading Edge of Personalized Medicine: Specific Examples of Clinical Situations Where Personalized Medicine and Companion Diagnostics is Appropriate and Being Deployed 195
15.10.1 EGFR Assay 195
15.10.2 Individualized Warfarin Therapy 196
15.10.3 UGT1A1 Molecular Assay for Camptosar 197
15.10.4 Response to Gleevec in Gastrointestinal Stromal Tumors 197
15.10.5 LabCorp, ARCA Personalized Medicine Deal for Cardiovascular Diseases 197
15.10.6 Osmetech Licenses Epidauros Biotechnologie AG CYP2D6 Biomarker to Push into Companion Diagnostics 198
15.11 Companion Diagnostics and Personalized Medicine: Qualitative and Quantitative Market Analysis 198
15.11.1 Market Analysis of Molecular Diagnostics and Companion Diagnostics and Personalized Medicine 198
15.11.2 Diagnostics vs. Pharmaceuticals 199
15.11.3 Molecular Diagnostic Market 200
15.11.4 Molecular Diagnostics Technology Platforms and their Impact on Personalized Medicine 202
15.12 Snapshot of Companion Diagnostics Industry Structure 204
15.13 The Case for Theranostics (Therapeutic/Companion Diagnostic) 205
15.14 Personalized Medicine Market Analysis-Market Survey Data Characterizing the Qualitative and Quantitative Industry Parameters 206
15.15 How the Market Segregates Today 207
15.16 Timeline for Impact of Various Segments in Personalized Medicine 208
15.17 Challenges for Personalized Therapeutics and Companion Diagnostics Development 210
15.18 Macro Trends in Personalized Medicine 210
15.19 Personalized Medicine and Companion Diagnostics: Industry SWOT Analysis 214
16. Cancer Biomarker Testing Sector and Company Analysis 216
16.1 Abbott Molecular, Inc. (Formerly Vysis, Inc.) 216
16.2 Agendia 218
16.3 AMDL, Inc. 218
16.4 Aureon Laboratories, Inc. 218
16.5 BioCurex 218
16.6 Biomarker Technologies 218
16.7 Biomedical Diagnostics LLC 218
16.8 Biomerica 219
16.9 Biomira, Inc. 219
16.10 Biomoda 219
16.11 Byk Gulden 219
16.12 Clarient 220
16.13 Correlogic Systems, Inc. 221
16.14 Cytogen Corporation 221
16.15 Dako (Formerly Dako Cytomation) 222
16.16 diaDexus 223
16.17 Diagnocure, Inc. (ImmunoCyt™/uCyt+™) 223
16.18 DxS Ltd. 224
16.19 Epigenomics 225
16.20 Exagen Diagnostics, Inc. 226
16.21 Genesis Genomics 227
16.22 Health Discovery Corporation 227
16.23 Immunicon 227
16.24 Ipsogen 228
16.25 InterGenetics 229
16.26 Miraculins, Inc. 230
16.27 Molecular Devices Inc. (Formerly Arcturus Bioscience, Inc.) 230
16.28 Myriad Genetics, Inc. 230
16.29 Orion Genomics 231
16.30 Power3 Medical Products 231
16.31 Qiagen N.V. 232
16.32 SuperArray Bioscience Corporation 232
16.33 Upstream Biosciences, Inc. 232
16.34 Ventana Medical Systems, Inc. 233
16.35 Veridex 233
16.36 Vermillion 234
17. Business Trends in the Industry 238
17.1 Industry Consolidation 238
17.2 Breath of Product Offering and Pricing 239
17.3 Government Regulation of Medical Devices 239
17.3.1 FDA Guidance on Drug Test Co-development 241
17.4 Strategic Business and Marketing Considerations 241
17.5 Commercial Opportunities in Cancer Markers 241
17.5.1 Licensing and Intellectual Property (IP) Constraints and how they will Impact New Product Development 242
17.6 Moderators of Growth 242
17.6.1 Roadblocks to Integrating Cancer Biomarkers into Clinical Practice 243
17.7 Biotechnology Industry Trends 243
17.8 Pharmaceutical Industry Trends 244
17.9 Acquisition, License Agreement, Partnerships 245
17.10 Legal Developments 248
17.11 Sales and Marketing Strategies for Tumor Marker Tests 249
17.11.1 North American Market 250
17.11.2 International Markets 251
17.11.2.1 Europe 251
17.11.2.2 Central and South America 252
17.11.2.3 Asia/Pacific 252
17.12 Product Commercialization 252
17.13 Reimbursement 253
17.14 Self Referral Rules 254
17.15 Health Insurance Portability and Accountability Act 255
17.16 Clinical Laboratory Improvement Amendments (CLIA) 255
17.17 In-Vitro Diagnostic Directive (IVDD) and Medical Device Regulations 256
17.18 FDA's Quality System Regulation (QSR) 257
17.19 FDA's OIVD on IVDMIAs 257
17.20 FDA's Qualification of Cancer Biomarkers 258
17.20.1 Regulatory Perspectives of Biomarker Validation 258
17.21 Genetic Tests and Medical Records 258
17.21.1 Laws against Genetic Discrimination 259
17.22 Medicare Reimbursement 260
17.22.1 Medicare Part B Spending Trends 260
17.23 Global Drivers of Clinical Laboratory Testing 262
17.24 Global Outlook for Cancer Biomarkers 262
17.24.1 Which Companies are Utilizing Cutting-Edge Technologies to Develop, Validate and Implement Cancer Biomarkers for Clinical Use? 263
17.24.2 What Impediments Still Exist to Incorporating Promising Research into Clinical Practice? 263
17.24.3 Which Biomarkers Show the Most Promise for Approval? 264
17.24.4 How can Regulatory Oversight Drive Approval and Adoption of New Techno