Advances in Cancer Research (eBook)

Front Cover 1
Advances in Cancer Research 3
Copyright Page 4
Contents 6
Contributors to Volume 96 12
Introduction 16
Genomics in Cancer Drug Discovery and Development 17
Chapters 1-6: Discovery of Cancer Diagnostics and New Therapeutic Targets 17
Chapter 8: Preclinical Models of Malignancy 18
Chapters 9-11: Translating Novel Targeted Therapies From Rodents to Man: Biomarkers to Monitor Drug Action 18
Chapters 12-13: the Socioeconomic and Regulatory Challenges of Novel Targeted Oncology Therapeutics 19
References 20
Chapter 1: Biomarker Discovery in Epithelial Ovarian Cancer by Genomic Approaches 21
I. Introduction 22
II. Genomic Approaches in Biomarker Discovery 25
Acknowledgments 38
References 38
Chapter 2: Mass Spectrometry: Uncovering the Cancer Proteome for Diagnostics 43
I. Current Cancer Biomarkers 44
II. Early Detection 45
III. The Need for New Diagnostic Strategies 47
IV. Mass Spectrometry 49
V. Mass Spectrometry-Based Diagnostics 52
VI. Current Limitations of Diagnostic Mass Spectrometry 57
VII. Suggestions for Future Progress 62
VIII. Future Direction 63
References 63
Chapter 3: Microarrays to Identify New Therapeutic Strategies for Cancer 71
I. Introduction 72
II. Microarray Technologies 72
III. Microarrays in Drug Development 79
IV. Microarrays to Direct the Use of Cancer Therapeutics 80
V. Identification of Therapeutic Targets in Distinct Disease Subtypes 85
VI. Conclusions 90
References 91
Chapter 4: The Application of siRNA Technology to Cancer Biology Discovery 95
I. Introduction 95
II. The Mechanism of RNAi 96
III. Transcriptional Gene Silencing by siRNAs 100
IV. siRNAs Delivery: Strategies and Difficulties 101
V. RNAi as Discovery Tool in Cancer Biology 104
VI. RNAi Screens 107
VII. Limitations of siRNAs as Cancer Therapeutics: Not Related to Delivery Problems 115
VIII. Summary 116
References 116
Chapter 5: Ribozyme Technology for Cancer Gene Target Identification and Validation 123
I. Brief Biology of Ribozymes 123
II. Ribozymes as Tools for Gene Inactivation 125
III. Ribozymes as Tools in Gene Target Discovery and Validation 129
IV. Ribozyme-Based Genomic Technology in Cancer Gene Target Discovery and Validation 133
V. Summary 157
Acknowledgments 159
References 159
Chapter 6: Cancer Cell-Based Genomic and Small Molecule Screens 165
I. Introduction 166
II. Drugs, Druggability, and Target Validation 167
III. Post-genomic Discovery of Novel Targets 168
IV. Small Molecule Screens in Oncology 175
V. Conclusions 187
References 188
Chapter 7: Tumor Antigens as Surrogate Markers and Targets for Therapy and Vaccines 195
I. Introduction: The Immune System and the Concept of Tumor Antigens 195
II. How Tumor Antigens Are Recognized 196
III. Cancer Antigens 199
IV. Novel TAA Identification Techniques 200
V. Effective Targeting of TAA in the Clinic 202
VI. TAAs as Therapeutic Targets 204
VII. Cancer Vaccines 204
VIII. Tumor Antigens and Cancer Vaccines 205
IX. Tumor Antigens as Surrogate Markers and Targets for Therapy and Vaccines 206
X. Summary and Future Directions 207
References 208
Chapter 8: Practices and Pitfalls of Mouse Cancer Models in Drug Discovery 211
I. Why Are Animal Models Needed? 211
II. Model Types: Tumor Locations 213
III. Tumor Models: Cell Types 218
IV. Study Endpoints 219
V. Animal Modeling in the Post-genomics Age 223
VI. Conclusions 227
References 227
Chapter 9: Pharmacodynamic Biomarkers for Molecular Cancer Therapeutics 233
I. Introduction 234
II. Types of Biomarkers 236
III. The Pharmacological Audit Trail 238
IV. Methodological Issues 240
V. Rationale for Use of PD Markers to Facilitate Drug Development 242
VI. The Need for Multidisciplinary and Broad-Based Collaborative Research and Development 249
VII. Biomarker Methodology 250
VIII. Examples of PD Biomarkers for Specific New Drug Classes 257
IX. Combining Chemotherapy with Molecularly Targeted Agents 272
X. Conclusions and Future Perspective 273
Acknowledgments 275
References 275
Chapter 10: Biomarker Assay Translation from Discovery to Clinical Studies In Cancer Drug Development: Quantification of Emerging Protein Biomarkers 289
I. Introduction 290
II. Biomarkers and Cancer Drug Development 292
III. Biomarker Research Challenges: Technology Translation 295
IV. Biomarker Research Challenges: Cultural and Process Translation 301
V. Clinical Qualification 311
VI. Conclusions and Perspectives 314
Acknowledgments 316
References 316
Chapter 11: Molecular Optical Imaging of Therapeutic Targets of Cancer 319
I. Introduction 320
II. Role of Molecular-Specific Optical Imaging of Carcinogenesis 322
III. Cancer Biomarkers and Therapeutic Targets 324
IV. Optical Technologies 326
V. Optically Active Contrast Agents 331
VI. Delivery of Contrast Agents In Vivo 342
VII. Molecular-Specific Optical Imaging 344
VIII. Future Directions: "Smart" Contrast Agents 351
IX. Conclusions 355
References 356
Chapter 12: Personalized Medicine for Cancer: From Molecular Signature to Therapeutic Choice 365
I. Summary 365
II. Introduction 366
III. Prevention and Screening 371
IV. Detecting Cancer 373
V. New Treatment Approaches 374
VI. The Development of Personalized Medicine 377
VII. Barriers to Innovation 381
VIII. Patient's Experience 383
IX. Conclusions 385
References 389
Chapter 13: Cancer Drug Approval in the United States, Europe, and Japan 391
I. USA 391
II. Europe 401
III. Japan 404
IV. Discussion 407
Index 413