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Until superior therapeutic treatments are developed to prevent, treat and cure cancer, the best means of reducing mortality and morbidity in a disease this complex is early detection and diagnosis. In the major solid cancer types such as lung, breast, colon and prostate, long-term survival rates drop precipitously once metastatis has occurred. The case is clear for development of biomarkers for early detection and screening tests for diseases such as breast, colon, ovarian and lung cancer. In addition, diagnostic measurement of cancer disease progression is essential to successful disease management. For these reasons, development of new and effective biomarkers for cancer detection and diagnosis is central to the cancer problem. The use of nucleic acid biomarker diagnostics have begun to answer these questions. Protein biomarkers are also useful. The purpose of this TriMark Publications report is to describe the specific segment of the cancer diagnostics market which develops new biomarker technology platforms for diagnosing and treating cancer. Biomarkers are useful in following the course of cancer and evaluating which therapeutic regimes are most effective for a particular type of cancer, as well as determining long-term susceptibility to cancer or recurrence. This study particularly examines those clinical measurement devices, and their reagents and supplies, which are meant to be used in hospitals, clinics, commercial laboratories and doctor's offices to diagnose and monitor cancer. The examination also provides an in-depth discussion of the application of biomarkers in developing novel targeted cancer therapeutics, their predication response and efficacy, as well as their use in diagnosis of cancer.

The main objectives of this analysis are:

• Identifying viable technology drivers for cancer biomarkers and related companion diagnostics through a comprehensive look at platform technologies including, probe-based nucleic acid assays, microarrays and sequencing, and mass spectroscopy.

• Obtaining a complete understanding of the new cancer biomarker diagnostic tests-i.e., predictive, screening, prognostic, monitoring, pharmacogenomic and theranostic-from their basic principles to their applications.

• Discovering growing market opportunities by identifying high-growth applications in different cancer diagnostic areas, focusing on the biggest and expanding markets in oncology (e.g., biomarkers for breast cancer and predictive biomarkers).

• Focusing on global industry development through an in-depth analysis of the major world markets for cancer diagnostics, including growth forecasts.

This analysis emphasizes companies that are actively developing and marketing new reagents and supplies for performing cancer biomarker diagnostics tests. It discusses the various market trends and opportunities using new biomarkers, while providing an in-depth analysis of market share, revenue forecasts, and market drivers and restraints. The comprehensive focus of the study, backed by strategic recommendations, enables companies to position their growth strategies to benefit from the changing market conditions and obtain maximum return on investment.

This study surveys biotech companies known for marketing, manufacturing or developing instruments and reagents for the clinical cancer diagnostics market, both in the U.S. and the world. Leading companies are discussed in-depth, with sections on the companies' histories, product lines, business and marketing analyses, and subjective commentary on the companies' market positions.

This report answers the questions:

• Which companies are utilizing cutting-edge technologies to develop, validate, and implement cancer biomarkers for clinical use?
• What impediments still exist to incorporating promising research into clinical practice?
• Which cancer biomarkers show the most promise for approval?
• What are the economic challenges to approval?
• How can regulatory oversight drive approval and adoption of new technologies?
• Which alliances show the greatest synergy in bringing valid biomarkers to market?
• Which shared technologies are driving the most encouraging development?

1. 1. Overview 12
2. 1.1 Statement of Report 12
3. 1.2 About This Report 12
4. 1.3 Scope of the Report 12
5. 1.4 Objectives 13
6. 1.5 Methodology 14
7. 1.6 Executive Summary 15
9. 2. Introduction to Cancer Biology and the Diagnostic Industry 17
10. 2.1 Biomarkers 17
11. 2.1.1 The Biomarker Market Drivers 17
12. 2.1.1.1 The Sector 17
13. 2.1.1.2 The Critical Path Opportunities 17
14. 2.1.1.3 The Capital Markets 17
15. 2.2 Cancer Detection and Treatment with Biomarkers 18
16. 2.2.1 The Problem 19
17. 2.3 Cancer: The Disease 21
18. 2.3.1 Metastasis 21
19. 2.3.2 Demographics and Statistics of Cancer 22
20. 2.4 Drivers of the Biotech and Diagnostics Industry 28
21. 2.4.1 Venture Funding of Biotech Sector 29
22. 2.4.2 Technological Innovation 30
23. 2.4.3 Government Funding 30
24. 2.4.4 Pharmaceutical Development and Bioanalytical Services 30
25. 2.4.5 The War on Cancer 32
26. 2.4.6 Current Oncology Drug Development 32
27. 2.5 Outlook for Tumor Markers 32
28. 2.6 Focus on Proteomics 35
29. 2.6.1 Scientific Background 35
30. 2.6.2 The Relationship between Proteins and Diseases 35
31. 2.6.3 Limitations of Existing Diagnostic Approaches 36
32. 2.6.4 Addressing the Heterogeneity of Cancer 36
33. 2.6.5 Validation of Biomarkers Through Proper Study Design 37
34. 2.6.6 Exploiting the Power of Mass Spectrometry to Improve Assay Specificity 37
35. 2.6.7 Creating and Maintaining a Multi-Disease Product Pipeline 39
36. 2.6.8 Partnerships for Developing Proteomic Biomarkers 39
37. 2.7 Epigenic Markers for Cancer 40
38. 2.8 Molecular Diagnostics Testing for Cancer 41
39. 2.9 Market Opportunities 41
40. 2.9.1 Industry Overview 42
41. 2.9.2 Medical Indications and Medically Useful Information 44
42. 2.9.3 Research Market 45
43. 2.9.4 Competition 46
44. 2.9.5 Diagnostic Services 46
45. 2.9.6 Clinical Image Analysis 46
46. 2.9.7 Research Imaging Market 46
47. 2.9.8 Genomic Disease Management and In Vitro Diagnostic Multivariate Index Assays (IVDMIA) 46
48. 2.9.9 Predictive Expression Profiles 47
50. 3. Market Analysis of the Cancer Biomarkers Space 48
51. 3.1 Scope of this Chapter 48
52. 3.2 The Overall Market Opportunity and Segmentation of the Total Cancer Biomarkers Marketplace 48
53. 3.3 Potential Cancer Biomarker Commercial Applications 51
54. 3.3.1 Market for Routine Tumor Markers 52
55. 3.3.2 Market for Genomic Cancer Biomarkers 57
56. 3.3.3 Market Size and Forecasts for Companion Diagnostic Tests for Cancer Therapeutics 59
57. 3.3.4 SWOT Analysis of the Major Cancer Biomarker Market Segments 61
58. 3.3.4.1 Traditional Serum Cancer Biomarkers 61
59. 3.3.4.2 Proteomic Cancer Biomarkers 62
60. 3.3.4.3 Companion Diagnostic Cancer Biomarkers 63
61. 3.4 Cancer Biomarker Market Estimates by Tissue of Origin 64
62. 3.4.1 Colorectal 64
63. 3.4.2 Prostate 65
64. 3.4.3 Lung 65
65. 3.4.4 Breast 65
66. 3.4.5 Ovarian 66
67. 3.5 Challenges Facing Cancer Biomarker Developers 66
68. 3.6 Unmet Product Needs in the Cancer Biomarkers Space 68
69. 3.7 Competitive Landscape of the Cancer Biomarkers Marketplace 70
71. 4. Major Clinical Applications of Cancer Biomarkers 73
72. 4.1 Launched Products and Pipeline 73
73. 4.2 CYP2C9 Pharmacogenetics and Role in Personalized Medicine 75
74. 4.3 Personalized Breast Cancer Therapy 75
75. 4.4 Personalized NSCLC Therapy 76
76. 4.5 AmpliChip®-based Personalized Medicine 76
78. 5. Breast Cancer 77
79. 5.1 Overview of Breast Cancer Disease 77
80. 5.2 BRCA1 and BRCA2 Genes 78
81. 5.2.1 Types of Genetic Testing Available for Breast Cancer 80
82. 5.2.1.1 DNA Sequencing 80
83. 5.2.1.2 Multi-Site Analysis 81
84. 5.2.1.3 Single-Site Analysis 81
85. 5.2.2 BRCA Test Results 81
86. 5.2.2.1 What Does a Positive BRCA1 or BRCA2 Test Result Mean? 81
87. 5.2.2.2 What Does a Negative BRCA1 or BRCA2 Test Result Mean? 81
88. 5.2.2.3 What Does an Ambiguous BRCA1 or BRCA2 Test Result Mean? 82
89. 5.2.2.4 What are the Options for a Person Who Tests Positive? 82
90. 5.2.3 What are Some of the Benefits of Genetic Testing for Breast Cancer Risk? 83
91. 5.2.4 What Are Some of the Risks of Genetic Testing for Breast and Ovarian Cancer Risk? 83
92. 5.3 Estrogen Receptors and Breast Cancer 83
93. 5.3.1 Expression and Prognostic Value of ER 83
94. 5.3.2 Progesterone Receptors and Breast Cancer 84
95. 5.3.3 ER and PR Predict Response to Endocrine Therapy 84
96. 5.4 HER2 Gene and Protein 85
97. 5.4.1 HER2 Tests 85
98. 5.4.1.1 IHC Test 85
99. 5.4.1.2 FISH Test 86
100. 5.4.1.3 Questions About Testing 88
101. 5.4.1.4 HER2 Tumor Status 89
102. 5.5 Herceptin® Treatment 89
103. 5.6 Tumor Assays for Adjuvant Chemotherapy 91
104. 5.7 Use of Genomics to Understand Breast Cancer 92
105. 5.8 Genetic Analysis Solution 93
106. 5.8.1 The Use of Proteomics in Breast Cancer 94
107. 5.8.2 Tissue Microarrays 95
108. 5.8.3 Protein Microarrays 97
109. 5.9 Gene Expression Microarrays and Recurrence Prediction 98
110. 5.9.1 Oncotype DX 99
111. 5.9.2 Oncotype DX for Breast Cancer 100
112. 5.9.3 Risk Assessment 100
113. 5.9.4 Use of Chemotherapy 100
114. 5.9.5 Utility of the Oncotype Test 100
115. 5.9.6 Clinical Development and Validation of Oncotype DX 101
116. 5.9.6.1 Clinical Development of the Oncotype DX Recurrence Score 101
117. 5.9.6.2 Clinical Validation of Prediction of Recurrence and Survival in N−, ER+ Patients Treated with Tamoxifen 101
118. 5.9.6.3 Oncotype DX Predicts the Likelihood of Recurrence 102
119. 5.9.6.4 Oncotype DX Predicts the Likelihood of Breast Cancer Survival in a Community Hospital Setting 102
120. 5.9.6.5 Oncotype DX Predicts both Prognosis and Tamoxifen Benefit 103
121. 5.10 Economic Benefits of Oncotype DX 103
122. 5.11 Increased Clinical Utility of Oncotype DX 104
123. 5.12 Second Generation Oncotype DX 105
124. 5.12.1 Recurrence and Benefit Test for N−, ER− Breast Cancer 105
125. 5.12.2 Taxane Benefit Test 105
126. 5.13 MammaPrint 105
127. 5.14 Rotterdam Signature 76-Panel 106
128. 5.15 Summary of Microarray Technologies 106
129. 5.16 Mass Spectrometry-based Approaches 107
130. 5.16.1 Gel-based Approaches 107
131. 5.16.2 Non-Gel-based Approaches 108
132. 5.16.2.1 SELDI-TOF MS 108
133. 5.16.2.2 SELDI and Prognosis 109
134. 5.16.2.3 SELDI and Treatment Monitoring 110
135. 5.16.3 Limitations of Mass Spectroscopy 110
136. 5.17 Outlook 111
137. 5.18 Future Perspectives 113
138. 5.19 Breast Cancer Program (NMP66) 114
139. 5.20 Myriad Genetics 114
140. 5.21 Veridex GeneSearch™ Breast Lymph Node 115
141. 5.22 OncoVue Cancer Risk Test 115
142. 5.23 Research Biomarkers for Breast Cancer 115
143. 5.24 Protein Biomarkers for Breast Cancer Prevention 116
144. 5.25 Biomarker Prognosis of Breast Cancer Treated with Doxorubicin 116
146. 6. Ovarian Cancer 117
147. 6.1 Serum Markers 119
148. 6.2 Biomarkers 120
149. 6.2.1 Strategies for Discovering New Cancer Biomarkers 121
150. 6.3 Serum Protein Biomarkers for Ovarian Cancer 121
151. 6.3.1 Clinical Proteomics 122
152. 6.4 Ovarian Cancer Triage Testing 123
153. 6.4.1 Vermillion's Ovarian Cancer Triage Diagnostic Program 124
155. 7. Prostate Cancer 126
156. 7.1 Overview 126
157. 7.1.1 Prevalence 126
158. 7.1.2 Prostate Cancer Progression and Recurrence Test 126
159. 7.1.3 Current Market Size 126
160. 7.2 Genes Involved in Prostate Cancer 127
161. 7.3 Androgen Independence 128
162. 7.4 Gene Markers in Prostate Cancer 129
163. 7.5 Microarray Gene Identification of Prostate Biomarkers 129
164. 7.6 GEArray DNA Microarrays 131
165. 7.7 Vermillion's Cancer Diagnostic Program 132
166. 7.8 Hepsin 132
167. 7.9 Matritech's Prostate Cancer Program (NMP48) 132
168. 7.10 Gen-Probe's PCA3 Assay 133
169. 7.11 Early Prostate Cancer Antigen-2 (EPCA-2) 133
170. 7.12 Mass Spectrometry 134
171. 7.13 Summary 136
173. 8. Bladder Cancer 137
174. 8.1 Overview 137
175. 8.1.1 Prevalence 137
176. 8.1.2 Progression and Recurrence 137
177. 8.1.3 Bladder Cancer Risk Factors 137
178. 8.1.4 Bladder Cancer Symptoms 137
179. 8.2 Bladder Cancer Tests 137
180. 8.3 UroVysion Bladder Cancer Kit 138
181. 8.4 Ikoniscope® Robotic Digital Microscopy Platform 139
182. 8.4.1 The CellOptics Platform 139
183. 8.4.2 Cell Staining and Genetic Characterization 139
184. 8.4.3 Ikoniscope/IkoniLAN Automated Microscopy 139
185. 8.5 Nuclear Matrix Protein Markers 140
186. 8.6 ImmunoCyt™/uCyt+™ 142
187. 8.7 Cangen Microsatellite DNA 144
188. 8.8 Bladder Cancer Market 144
189. 8.8.1 Urologist Market 144
190. 8.8.2 Clinical Lab Market 144
191. 8.8.3 Primary Care Market 144
192. 8.8.4 Private and Public Sector Markets 145
193. 8.8.5 POC Market 145
194. 8.8.6 Market Distribution 145
195. 8.8.7 Reimbursement 145
197. 9. Colorectal Cancer 146
198. 9.1 Overview 146
199. 9.1.1 Prevalence 146
200. 9.1.2 Progression and Recurrence 146
201. 9.2 Screening for CRC 148
202. 9.2.1 Stool-based DNA (sDNA) Screening 149
203. 9.3 Almac Diagnostics DSA 150
204. 9.4 Colon Cancer Program (NMP35) 151
205. 9.5 Myriad Genetics Colaris AP Risk Assessment 151
206. 9.6 Summary 152
208. 10. Genetic Diagnostics Set to Revolutionize Cancer Diagnostic Testing 153
209. 10.1 Overview 153
210. 10.1.1 Clinicians Need for More Information with Regard to Therapeutic Treatment Drives Demand for Pharmacogenomic Testing 153
211. 10.1.2 Predictive Medicine Shows Potential for Genetic Diagnostics 153
212. 10.1.3 Different Rates of Growth 154
213. 10.1.4 Effective Competitive Strategies 154
214. 10.1.5 Improvements in Marketing Effectiveness 154
215. 10.1.6 Emerging Technologies Imply Start of a New Era and Offer Tremendous Growth Opportunities 154
216. 10.1.7 Increased Market Share 154
217. 10.1.8 Technologies Used in Genetic Testing 154
218. 10.2 AMAS Test 155
219. 10.3 Corixa Antibodies as Tumor Markers 155
220. 10.4 Cytovision 156
221. 10.5 Ariol System 156
222. 10.6 Mammaglobin Protein Expression 156
223. 10.7 L523S or KOC RNA Binding Protein 156
224. 10.8 CA1-18 from EDP Biotech 157
226. 11. Leukemia Biomarkers 158
227. 11.1 Overview 158
228. 11.1.1 Prevalence 158
229. 11.1.1.1 Progression and Recurrence 158
231. 12. Lung Cancer 159
233. 13. Enabling Technologies for Oncology Biomarker Discovery 160
234. 13.1 Automated Cellular Imaging System (ACIS®) 160
235. 13.1.1 ACIS for HER2 Protein Expression Testing 161
236. 13.1.2 ACIS for ER Protein Expression Testing 161
237. 13.1.3 ACIS for PR Protein Expression Testing 161
238. 13.1.4 ACIS for Cell Proliferation Expression 162
239. 13.1.5 ACIS for Protein Expression 162
240. 13.1.6 ACIS for Protein Micrometastases in Bone Marrow 162
241. 13.1.7 ACIS for Protein Micrometastases in Tissue 162
242. 13.1.8 ACIS for Tissue Microarray 162
243. 13.1.9 ACIS for DNA Ploidy 162
244. 13.1.10 ACIS for HPV 162
245. 13.2 DNA Methylation 163
246. 13.2.1 Differential Methylation Hybridization (DMH) 163
247. 13.2.2 MIRA-Assisted Microarrays for DNA Methylation Analysis and Cancer Diagnosis 163
248. 13.3 Proteomics 164
249. 13.3.1 Proteomics Technologies for Cancer Marker Discovery 164
250. 13.3.2 Validation of Candidate Biomarkers 165
251. 13.3.3 Requirements Bringing a New Marker into the Market 165
252. 13.3.4 Value Chain in the Development of New Cancer Biomarkers 166
253. 13.4 Secreted Proteins as Cancer Biomarkers 166
254. 13.4.1 Markers of Known Tissue Origin 166
255. 13.4.2 Secreted Proteins as Low Abundance Markers 166
256. 13.4.3 Secreted Proteins in Tissue and Blood 166
257. 13.5 Noncodings RNA as Potential Tumor Markers 166
258. 13.5.1 miRNA Meets Microarray 167
259. 13.5.2 Mimetics and Inhibitors 167
260. 13.5.3 Clinical Patterns in Cancer 167
261. 13.6 Architect TIMP-1 (Tissue Inhibitor of Metalloproteinases-1) Immunoassay for Colorectal Cancer Detection 167
262. 13.7 Companies Developing Automated Microscope-based Analysis Systems 167
263. 13.8 Companies Developing Research Products for Tumor Cell Isolation 168
264. 13.9 Companies Supplying Fluorescently Labeled Antibodies to Characterize Tumor Cells 168
265. 13.10 PerkinElmer High Throughput Platforms: AlphaScreen®, AequoScreen®, DELFIA® and LANCE® Technologies 168
267. 14. Biomarker Tests Co-developed with Cancer Therapeutics as Companion Diagnostics 169
268. 14.1 Sector Overview 169
269. 14.2 Companion Diagnostics 171
270. 14.3 EGFR for Colorectal Cancer and Camptostar (Irinotecan) 171
271. 14.4 EGFR Express and Erbitux (Cetuximab) 172
272. 14.5 HER2 and Heceptin 172
273. 14.6 Myriad's TheraGuide 5-FU 172
274. 14.7 TheraScreen: EGFR29 173
275. 14.8 Drivers and Barriers to Companion Diagnostics 173
276. 14.9 Partnerships with Pharma Companies to Identify Therapeutic Targets 174
277. 14.10 Future Developments for Companion Diagnostics 174
279. 15. Companion Diagnostics and Personalized Medicine: Biology, Approaches, Pipeline and Regulatory Trends 176
280. 15.1 Scope of this Chapter 176
281. 15.2 Introduction to Companion Diagnostics and Personalized Medicine 176
282. 15.3 The Compelling Case for Personalized Medicine 178
283. 15.4 Drug Metabolism and Implications for Companion Diagnostics and Personalized Medicine 179
284. 15.5 Examples of Personalized Medicine 183
285. 15.6 Personalized Medicine and Companion Diagnostics Testing Product Pipeline 185
286. 15.7 The Personalized Medicine Coalition 187
287. 15.8 Regulatory Trends and Guidelines in the Personalized Medicine Space 189
288. 15.8.1 The Changing Regulatory Landscape for Personalized Medicine 191
289. 15.9 Patenting Personalized Medicine 192
290. 15.10 The Leading Edge of Personalized Medicine: Specific Examples of Clinical Situations Where Personalized Medicine and Companion Diagnostics is Appropriate and Being Deployed 194
291. 15.10.1 EGFR Assay 195
292. 15.10.2 Individualized Warfarin Therapy 195
293. 15.10.3 UGT1A1 Molecular Assay for Camptosar 196
294. 15.10.4 Response to Gleevec in Gastrointestinal Stromal Tumors 196
295. 15.10.5 LabCorp, ARCA Personalized Medicine Deal for Cardiovascular Diseases 197
296. 15.10.6 Osmetech Licenses Epidauros Biotechnologie AG CYP2D6 Biomarker to Push into Companion Diagnostics 197
297. 15.11 Companion Diagnostics and Personalized Medicine: Qualitative and Quantitative Market Analysis 197
298. 15.11.1 Market Analysis of Molecular Diagnostics and Companion Diagnostics and Personalized Medicine 197
299. 15.11.2 Diagnostics vs. Pharmaceuticals 198
300. 15.11.3 Molecular Diagnostic Market 199
301. 15.11.4 Molecular Diagnostics Technology Platforms and their Impact on Personalized Medicine 201
302. 15.12 Snapshot of Companion Diagnostics Industry Structure 203
303. 15.13 The Case for Theranostics (Therapeutic/Companion Diagnostic) 204
304. 15.14 Personalized Medicine Market Analysis-Market Survey Data Characterizing the Qualitative and Quantitative Industry Parameters 205
305. 15.15 How the Market Segregates Today 206
306. 15.16 Timeline for Impact of Various Segments in Personalized Medicine 207
307. 15.17 Challenges for Personalized Therapeutics and Companion Diagnostics Development 209
308. 15.18 Macro Trends in Personalized Medicine 209
309. 15.19 Personalized Medicine and Companion Diagnostics: Industry SWOT Analysis 213
311. 16. Cancer Biomarker Testing Sector and Company Analysis 215
312. 16.1 Abbott Molecular, Inc. (Formerly Vysis, Inc.) 215
313. 16.2 Agendia 217
314. 16.3 AMDL, Inc. 217
315. 16.4 Aureon Laboratories, Inc. 217
316. 16.5 BioCurex 217
317. 16.6 Biomarker Technologies 217
318. 16.7 Biomedical Diagnostics LLC 217
319. 16.8 Biomerica 218
320. 16.9 Biomira, Inc. 218
321. 16.10 Biomoda 218
322. 16.11 Byk Gulden 218
323. 16.12 Clarient 219
324. 16.13 Correlogic Systems, Inc. 220
325. 16.14 Cytogen Corporation 220
326. 16.15 Dako (Formerly Dako Cytomation) 221
327. 16.16 diaDexus 222
328. 16.17 Diagnocure, Inc. (ImmunoCyt™/uCyt+™) 222
329. 16.18 DxS Ltd. 223
330. 16.19 Epigenomics 224
331. 16.20 Exagen Diagnostics, Inc. 225
332. 16.21 Genesis Genomics 226
333. 16.22 Health Discovery Corporation 226
334. 16.23 Immunicon 226
335. 16.24 Ipsogen 227
336. 16.25 InterGenetics 228
337. 16.26 Miraculins, Inc. 229
338. 16.27 Molecular Devices Inc. (Formerly Arcturus Bioscience, Inc.) 229
339. 16.28 Myriad Genetics, Inc. 229
340. 16.29 Orion Genomics 230
341. 16.30 Power3 Medical Products 230
342. 16.31 Qiagen N.V. 231
343. 16.32 SuperArray Bioscience Corporation 231
344. 16.33 Upstream Biosciences, Inc. 231
345. 16.34 Ventana Medical Systems, Inc. 232
346. 16.35 Veridex 232
347. 16.36 Vermillion 233
349. 17. Business Trends in the Industry 237
350. 17.1 Industry Consolidation 237
351. 17.2 Breadth of Product Offering and Pricing 238
352. 17.3 Government Regulation of Medical Devices 238
353. 17.3.1 FDA Guidance on Drug Test Co-development 240
354. 17.4 Strategic Business and Marketing Considerations 240
355. 17.5 Commercial Opportunities in Cancer Markers 240
356. 17.5.1 Licensing and Intellectual Property (IP) Constraints and how they will Impact New Product Development 241
357. 17.6 Moderators of Growth 241
358. 17.6.1 Roadblocks to Integrating Cancer Biomarkers into Clinical Practice 242
359. 17.7 Biotechnology Industry Trends 242
360. 17.8 Pharmaceutical Industry Trends 243
361. 17.9 Acquisition, License Agreement, Partnerships 244
362. 17.10 Legal Developments 247
363. 17.11 Sales and Marketing Strategies for Tumor Marker Tests 248
364. 17.11.1 North American Market 249
365. 17.11.2 International Markets 250
366. 17.11.2.1 Europe 250
367. 17.11.2.2 Central and South America 251
368. 17.11.2.3 Asia/Pacific 251
369. 17.12 Product Commercialization 251
370. 17.13 Reimbursement 252
371. 17.14 Self Referral Rules 253
372. 17.15 Health Insurance Portability and Accountability Act 254
373. 17.16 Clinical Laboratory Improvement Amendments (CLIA) 254
374. 17.17 In-Vitro Diagnostic Directive (IVDD) and Medical Device Regulations 255
375. 17.18 FDA's Quality System Regulation (QSR) 256
376. 17.19 FDA's OIVD on IVDMIAs 256
377. 17.20 FDA's Qualification of Cancer Biomarkers 257
378. 17.20.1 Regulatory Perspectives of Biomarker Validation 257
379. 17.21 Genetic Tests and Medical Records 257
380. 17.21.1 Laws against Genetic Discrimination 258
381. 17.22 Medicare Reimbursement 259
382. 17.22.1 Medicare Part B Spending Trends 259
383. 17.23 Global Drivers of Clinical Laboratory Testing 261
384. 17.24 Global Outlook for Cancer Biomarkers 261
385. 17.24.1 Which Companies are Utilizing Cutting-Edge Technologies to Develop, Validate and Implement Cancer Biomarkers for Clinical Use? 262
386. 17.24.2 What Impediments Still Exist to Incorporating Promising Research into Clinical Practice? 262
387. 17.24.3 Which Biomarkers Show the Most Promise for Approval? 263
388. 17.24.4 How can Regulatory Oversight Drive Approval and Adoption of New Technologies? 263
389. 17.24.5 Which Alliances Show the Greatest Synergy in Bringing Valid Biomarkers to Market? 263
390. 17.24.6 Which Shared Technologies are Driving the Most Encouraging Development? 263
391. 17.24.7 How Strategic Alliances and Interdisciplinary Involvement Drive Development and Implementation of Emerging Biomarker Technologies 264
392. 17.25 Oncology Biomarker Qualification Initiative 264
393. 17.26 FDA Critical Path 265
394. 17.27 FDA Criteria for a Valid Biomarker 265
396. 18. Companies Entering the Cancer Diagnostics Market with Novel Technology Platforms 266
397. 18.1 Abbott Diagnostics 266
398. 18.2 Affymetrix, Inc. 268
399. 18.3 Agendia BV 270
400. 18.4 Agensys, Inc. 271
401. 18.5 Almac Group 271
402. 18.6 AMDL, Inc. 271
403. 18.7 Aureon Laboratories, Inc. 273
404. 18.8 Bayer Diagnostics Corporation 274
405. 18.9 Beckman Coulter, Inc. 274
406. 18.10 Biocode S.A. 275
407. 18.11 BioCurex, Inc. 276
408. 18.12 Biomarker Technologies LLC 276
409. 18.13 Biomedical Diagnostics LLC 276
410. 18.14 Biomerica 276
411. 18.15 bioMérieux 277
412. 18.16 Biomira, Inc. 277
413. 18.17 Biomoda, Inc. 278
414. 18.18 Bruker Daltonics, Inc. 279
415. 18.19 Byk Gulden 279
416. 18.20 Cangen Biotechnologies, Inc. 279
417. 18.21 Caprion Proteomics 281
418. 18.22 Celera Diagnostics 281
419. 18.23 Cepheid 282
420. 18.24 Clarient, Inc. 283
421. 18.25 Claros Diagnostics, Inc. 284
422. 18.26 Clinical Data, Inc.: PGxHealth and Cogenics 284
423. 18.27 Correlogic Systems, Inc. 285
424. 18.28 CytoCore (Formerly Molecular Diagnostics, Inc.) 286
425. 18.29 Cytogen Corporation 286
426. 18.30 Dako (Formerly Dako Cytomation) 289
427. 18.31 diaDexus LLC 290
428. 18.32 DiagnoCure, Inc. 291
429. 18.33 Diagnostic Products Corporation 292
430. 18.34 Diagnostic Systems Laboratories, Inc. 292
431. 18.35 Digene Corporation 292
432. 18.36 DRG International, Inc. 293
433. 18.37 DxS Ltd. 293
434. 18.38 EDP Biotech Corporation 294
435. 18.39 Eisai Co., Ltd. 295
436. 18.40 Epigenomics 295
437. 18.41 Exact Sciences Corporation 296
438. 18.42 Exagen Diagnostics, Inc. 296
439. 18.43 Gene Logic, Inc. 297
440. 18.44 Genesis Genomics, Inc. 298
441. 18.45 Genomic Health, Inc. 298
442. 18.46 Gen-Probe, Inc. 298
443. 18.47 Health Discovery Corporation 299
444. 18.48 Hologic, Inc. (Formerly Cytyc Corporation) 300
445. 18.49 Ikonisys, Inc. 300
446. 18.50 Immunicon Corporation 301
447. 18.51 Immunomedics, Inc. 305
448. 18.52 Incyte Pharmaceuticals, Inc. 306
449. 18.53 InterGenetics® 306
450. 18.54 Ipsogen 306
451. 18.55 LabCorp® 307
452. 18.56 Matritech, Inc. 308
453. 18.57 Miraculins, Inc. 310
454. 18.58 Mitsubishi Kagaku Medical 311
455. 18.59 Molecular Devices (Formerly Arcturus Biosciences, Inc.) 311
456. 18.60 Myriad Genetics, Inc. 311
457. 18.61 NimbleGen Systems, Inc. 316
458. 18.62 Northwest Biotherapeutics, Inc. 316
459. 18.63 Oncotech, Inc. 317
460. 18.64 Orion Genomics 318
461. 18.65 Oxford Genome Sciences 318
462. 18.66 Panacea Pharmaceuticals, Inc. 319
463. 18.67 Phenomenone Discoveries 319
464. 18.68 Polymedco, Inc. 319
465. 18.69 Power3 Medical Products 320
466. 18.70 Proteome Systems Ltd. 320
467. 18.71 Qiagen N.V. 321
468. 18.72 Sanko Junyaku Co., Ltd. 322
469. 18.73 SensiGen LLC 322
470. 18.74 SuperArray Bioscience Corporation 322
471. 18.75 Third Wave Technologies, Inc. 322
472. 18.76 Tosoh Medics, Inc. 323
473. 18.77 TriPath Imaging, Inc. 323
474. 18.78 Upstream Biosciences, Inc. 325
475. 18.79 Ventana Medical Systems, Inc. 325
476. 18.80 Veridex LLC 326
477. 18.81 Vermillion, Inc. (Formerly Ciphergen) 327
479. Appendix 1: Cancer Biomarker Centers of Research 330
481. Appendix 2: Myriad Patents on Genes BRAC1 and BRAC2 331
483. Appendix 3: Common Laboratory Tests for Cancer 332
485. Appendix 4: Questions/Issues in the Cancer Biomarkers Space 339
487. Appendix 5: Cancer Markers Currently in Common Clinical Use 341
489. Appendix 6: International Federation of Gynecology and Obstetrics (FIGO) Staging System for Primary Carcinoma of the Ovary 342
491. Appendix 7: FDA Guidance for Industry: Pharmacogenomic Data Submission 343
492. A7.1 Introduction 343
493. A7.2 Background 343
494. A7.3 Submission Policy 344
495. A7.3.1 General Principles 344
496. A7.3.2 Specific Uses of Pharmacogenomic Data in Drug Development and Labeling 346
497. A7.3.3 Benefits of Voluntary Submissions to Sponsors and FDA 347
498. A7.4 Submission of Pharmacogenomic Data 348
499. A7.4.1 Submission of Pharmacogenomic Data During the IND Phase 348
500. A7.4.2 Submission of Pharmacogenomic Data to a New NDA, BLA, or Supplement 349
501. A7.4.3 Submission to a Previously Approved NDA or BLA 350
502. A7.4.4 Compliance with 21 CFR Part 58 350
503. A7.4.5 Submission of Voluntary Genomic Data from Application-Independent Research 351
504. A7.5 Format and Content of a VGDS 351
505. A7.6 Process for Submitting Pharmacogenomic Data 352
506. A7.7 Agency Review of VGDSs 352
508. Glossary 354
511. INDEX OF FIGURES
513. Figure 3.1: Potential Market for Cancer Biomarkers, 2006 48
514. Figure 3.2: Segmentation of the Cancer biomarkers Marketplace Based Upon Commercial Offerings-Products and Services 51
515. Figure 3.3: Geographical Distribution of Cancer Tumor Diagnostic Testing 55
516. Figure 3.4: Cancer Biomarkers Research Market, 2006-2011 60
517. Figure 3.5: Breast Cancer Biomarker Market Potential, 2005 66
518. Figure 3.6: Challenges in the Study or Utilization of Proteomic Cancer Biomarkers 67
519. Figure 3.7: Challenges in the Study or Utilization of Companion Diagnostic Cancer Biomarkers 67
520. Figure 3.8: Challenges in the Study or Utilization of Serum Cancer Markers 68
521. Figure 3.9: Top Unmet Needs in Commercial Products in the Cancer Biomarkers Space 69
522. Figure 5.1: Hybridization Process 86
523. Figure 5.2: FISH Test Procedure 87
524. Figure 5.3: Gene Expression Profiling 97
525. Figure 15.1: Phase I and II Processes of Drug Metabolism 179
526. Figure 15.2: Human Phase I Enzymes 180
527. Figure 15.3: Human Phase II Enzymes 180
528. Figure 15.4: Hepatic Distribution of Human CYP450 181
529. Figure 15.5: Relative Contribution of CYP450 Enzymes to Drug Metabolism 181
530. Figure 15.6: Genetic Components Determine Drug Metabolism 182
531. Figure 15.7: From Genetic Content to Personalized Medicine 198
532. Figure 15.8: Remuneration for Diagnostics 198
533. Figure 15.9: Breakout of the Molecular Diagnostics Marketplace 199
534. Figure 15.10: Molecular Diagnostics Market Segmentation 200
535. Figure 15.11: Molecular Diagnostics Market Segmentation by Technology 201
536. Figure 15.12: Market Survey Respondent Demographics 205
537. Figure 15.13: Breakout of the Respondent Pool by Affiliation 206
538. Figure 15.14: Segmentation of the Personalized Medicine Market 206
539. Figure 15.15: Personalized Medicine Market Drivers 210
540. Figure 15.16: Challenges in the Personalized Medicine Space 211
541. Figure 16.1: Epigenomics Product Development Pipeline 225
542. Figure 17.1: Medicare Part B Spending on Clinical Laboratory Services, 1991-2005 259
545. INDEX OF TABLES
547. Table 2.1: Cancer Biomarkers at the Nexus Point 19
548. Table 2.2: Drug Development by Type of Cancer 22
549. Table 2.3: Organ Specific Medicines in Development for Cancer, 2006 23
550. Table 2.4: Estimates for the Leading Sites of New Cancer Cases and Deaths in the U.S. by Sex, 2007 24
551. Table 2.5: Estimated Worldwide Number of New Cancer Cases and Deaths by Type of Cancer 24
552. Table 2.6: Estimated Number of New Cancer Cases and Deaths by Region 25
553. Table 2.7: Cancer Death Rates per 100,000 Population (and Rank) for All Cancer Sites by Country 26
554. Table 2.8: Cancer Associated Genes 27
555. Table 2.9: Carcinogens in the Workplace 27
556. Table 2.10: Cancer Biomarker Markets 28
557. Table 2.11: Private Funding Levels for the Biotechnology Segment, 1995-2006 29
558. Table 2.12: Global Pharmaceutical Industry R&D Spending, 1995-2006 31
559. Table 2.13: U.S. Government NIH Research Budget, 1995-2007 31
560. Table 2.14: Tumor Markers Currently in Common Use 33
561. Table 2.15: Herceptin Worldwide Sales, 1999-2007 34
562. Table 2.16: Classes of Drugs Used to Treat Breast Cancer 34
563. Table 2.17: Solutions to Biomarker Developments 36
564. Table 2.18: Vermillion Collaborations 39
565. Table 2.19: Uses of Molecular Diagnostics in Detection and Management of Cancer 41
566. Table 2.20: U.S. Cancer Diagnostic Testing Market Size, 2005-2012 43
567. Table 2.21: Market Opportunities for Cancer Biomarker Technology Platforms 44
568. Table 3.1: Characteristics of Different Cancer Biomarker Types and Associated Market Opportunities 50
569. Table 3.2: Segmentation of the Cancer Biomarker Market by Type/Lineage of Cancer Biomarkers and Market Size 50
570. Table 3.3: In Vitro Cancer Marker Market Segments Worldwide, 2001 and 2007 52
571. Table 3.4: Worldwide Market Size in Dollar Volume for Tumor Marker Assays Product Market, 2001-2010 52
572. Table 3.5: U.S. Market Size in Dollar Volume for Tumor Marker Assays Product Market, 2001-2010 53
573. Table 3.6: Worldwide In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010 53
574. Table 3.7: U.S. In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010 53
575. Table 3.8: Japanese In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010 54
576. Table 3.9: European In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010 54
577. Table 3.10: Global Distribution of IVD Cancer Tumor Marker Diagnostic Testing, 2005 54
578. Table 3.11: Estimated Market Share of Major Competitors in U.S. Cancer Tumor Marker Diagnostics Market 55
579. Table 3.12: Major Presence in Cancer Tumor Marker Diagnostics Markets 55
580. Table 3.13: Worldwide CEA Sales, 2001-2010 56
581. Table 3.14: U.S. CEA Sales, 2001-2010 57
582. Table 3.15: Cancer Genomic Biomarker Markets, 2002-2012 57
583. Table 3.16: Cancer Biomarkers Research Market Forecast, 2006-2011 60
584. Table 3.17: Cancer Biomarker Market Estimates by Tissue of Origin 64
585. Table 3.18: Companies Developing New Proteomic Cancer Biomarker Technology Platforms 72
586. Table 4.1: Cancer Biomarkers Used to Maximize Likelihood of Response 74
587. Table 4.2: Biomarkers for Monitoring Therapeutic Effectiveness and Resistance 74
588. Table 4.3: Biomarkers for Dose Response of Therapy 74
589. Table 4.4: Decision on Optimal Duration of Therapy 74
590. Table 5.1: U.S. Breast Cancer Rate Decline, 2002-2006 77
591. Table 5.2: BRCA Development Model 79
592. Table 5.3: BRCA Test Development and Commercialization 80
593. Table 5.4: BRAC Analysis 80
594. Table 5.5: Revenue for BRACAnalysis® Risk Assessment Test, 2002-2006 80
595. Table 5.6: GEArray DNA Microarrays and RT2 Profiler PCR Arrays 97
596. Table 5.7: Product Development Opportunities in Breast Cancer 104
597. Table 5.8: Concentration of Some Abundant Proteins, New Cancer Biomarkers Identified by SELDI-TOF, and Classical Cancer Biomarkers in Serum 111
598. Table 5.9: Questions Related to Diagnostic SELDI-TOF Technology 113
599. Table 6.1: Worldwide CA-125 Sales, 2001-2010 117
600. Table 6.2: U.S. CA-125 Sales, 2001-2010 118
601. Table 6.3: Some Clinically Established Cancer Serum Markers Currently in Use for Cancer 119
602. Table 6.4: Pathophysiology of Ovarian Cancer and Characterization of Ovarian Epithelial Tumors 125
603. Table 7.1: Worldwide PSA Sales, 2000-2010 127
604. Table 7.2: U.S. PSA Sales, 2000-2010 127
605. Table 7.3: Molecular Gene Markers for Prostate Cancer 129
606. Table 8.1: Worldwide Bladder Cancer Marker Sales, 2001-2010 141
607. Table 8.2: U.S. Bladder Cancer Marker Sales, 2001-2010 141
608. Table 8.3: Worldwide NMP22 Sales, 2001-2010 142
609. Table 8.4: Summary of Matritech's Product Development Programs 143
610. Table 8.5: Opportunities for Bladder Cancer Biomarkers 144
611. Table 9.1: TNM Staging for Colorectal Cancer 147
612. Table 10.1: Genetic Diagnostics Market, 2004-2012 153
613. Table 13.1: Genomic and Proteomic Technologies 165
614. Table 14.1: Potential Benefits of Biomarkers as Companion Diagnostics 171
615. Table 14.2: Utility of Biomarker as Companion Diagnostics to Drug Development 171
616. Table 14.3: Device Submission Elements for the FDA 174
617. Table 14.4: Summary of Biomarker Use in the Commercialization of Novel Oncology Pharmacotherapeutics 175
618. Table 14.5: Pharmacoeconomic Challenges to the Implementation of Biomarkers as Companion Diagnostic Tests 175
619. Table 15.1: Percentage of Non-Responders in Various Drug Classes 178
620. Table 15.2: High Profile Drug Withdrawals from the Marketplace 178
621. Table 15.3: Drug Metabolism Drives Drug Efficacy/Toxicity 183
622. Table 15.4: Population Frequency of the Various Cytochromes 183
623. Table 15.5: Selected List of Personalized Medicine Tests 185
624. Table 15.6: Personalized Medicine and Companion Diagnostics Product Pipeline 186
625. Table 15.7: Marketed Personalized Therapies, 2006 187
626. Table 15.8: Various Molecular Diagnostics Technologies: Timeline for Impact 201
627. Table 15.9: Various Molecular Diagnostics Technologies: Impact on Different Therapeutic Areas in Personalized Medicine 202
628. Table 15.10: Various Molecular Diagnostics Technologies: Technical Challenges in the Deployment for Personalized Medicine 202
629. Table 15.11: Classification of Diagnostics by Risk 204
630. Table 15.12: Areas in Personalized Medicine-Timeline of Impact 207
631. Table 15.13: Impact of Personalized Medicine on Various Therapeutic Areas 208
632. Table 15.14: Hurdles in Personalized Medicine and Companion Diagnostics Development in Various Therapeutic Areas 209
633. Table 15.15: Market Opportunities in Personalized Medicine 212
634. Table 15.16: Challenges for Market Adoption of the Various Personalized Medicine Tests 213
635. Table 15.17: Personalized Medicine Industry SWOT 214
636. Table 16.2: Clarient Revenue, 2002-2006 219
637. Table 16.3: Clarient Percentage of Revenue, 2004-2006 219
638. Table 16.4: Opportunities for Biomarkers in Cancer Diagnosis and Treatment 220
639. Table 16.5: Myriad Biomarker Revenue, 2002-2006 230
640. Table 17.1: List and Discounted Prices for Abbott Tumor Marker Tests 238
641. Table 17.2: Hospital Laboratory Share of Part B Medicare Spending, 1996-2005 259
642. Table 17.3: Medicare Spending on Clinical Lab Services, 1991-2005 260
643. Table 17.4: Medicare Part B Spending Per Medicare Enrollee, 1998-2005 260
644. Table 18.1: Tumor Diagnosis Immunoassay 293
645. Table 18.2: Tumor Diagnosis Radioimmunoassay 293
646. Table 18.3: Summary of Matritech's Product Development Programs 310
647. Table A1: Team Descriptions 330
648. Table A5: Cancer Markers in Use 341