Genomics in Cancer Drug Discovery and Development
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Table of contents
- Advances in Cancer Researchii
- Copyright Pageiii
- Contentsv
- Contributors to Volume 96xi
- Introductionxv
- Genomics in Cancer Drug Discovery and Developmentxvi
- Chapters 1-6: Discovery of Cancer Diagnostics and New Therapeutic Targetsxvi
- Chapter 8: Preclinical Models of Malignancyxvii
- Chapters 9-11: Translating Novel Targeted Therapies From Rodents to Man: Biomarkers to Monitor Drugxvii
- Chapters 12-13: the Socioeconomic and Regulatory Challenges of Novel Targeted Oncology Therapeuticsxviii
- Referencesxix
- Chapter 1: Biomarker Discovery in Epithelial Ovarian Cancer by Genomic Approaches1
- I. Introduction2
- II. Genomic Approaches in Biomarker Discovery5
- Acknowledgments18
- References18
- Chapter 2: Mass Spectrometry: Uncovering the Cancer Proteome for Diagnostics23
- I. Current Cancer Biomarkers24
- II. Early Detection25
- III. The Need for New Diagnostic Strategies27
- IV. Mass Spectrometry29
- V. Mass Spectrometry-Based Diagnostics32
- VI. Current Limitations of Diagnostic Mass Spectrometry37
- VII. Suggestions for Future Progress42
- VIII. Future Direction43
- References43
- Chapter 3: Microarrays to Identify New Therapeutic Strategies for Cancer51
- I. Introduction52
- II. Microarray Technologies52
- III. Microarrays in Drug Development59
- IV. Microarrays to Direct the Use of Cancer Therapeutics60
- V. Identification of Therapeutic Targets in Distinct Disease Subtypes65
- VI. Conclusions70
- References71
- Chapter 4: The Application of siRNA Technology to Cancer Biology Discovery75
- I. Introduction75
- II. The Mechanism of RNAi76
- III. Transcriptional Gene Silencing by siRNAs80
- IV. siRNAs Delivery: Strategies and Difficulties81
- V. RNAi as Discovery Tool in Cancer Biology84
- VI. RNAi Screens87
- VII. Limitations of siRNAs as Cancer Therapeutics: Not Related to Delivery Problems95
- VIII. Summary96
- References96
- Chapter 5: Ribozyme Technology for Cancer Gene Target Identification and Validation103
- I. Brief Biology of Ribozymes103
- II. Ribozymes as Tools for Gene Inactivation105
- III. Ribozymes as Tools in Gene Target Discovery and Validation109
- IV. Ribozyme-Based Genomic Technology in Cancer Gene Target Discovery and Validation113
- V. Summary137
- Acknowledgments139
- References139
- Chapter 6: Cancer Cell-Based Genomic and Small Molecule Screens145
- I. Introduction146
- II. Drugs, Druggability, and Target Validation147
- III. Post-genomic Discovery of Novel Targets148
- IV. Small Molecule Screens in Oncology155
- V. Conclusions167
- References168
- Chapter 7: Tumor Antigens as Surrogate Markers and Targets for Therapy and Vaccines175
- I. Introduction: The Immune System and the Concept of Tumor Antigens175
- II. How Tumor Antigens Are Recognized176
- III. Cancer Antigens179
- IV. Novel TAA Identification Techniques180
- V. Effective Targeting of TAA in the Clinic182
- VI. TAAs as Therapeutic Targets184
- VII. Cancer Vaccines184
- VIII. Tumor Antigens and Cancer Vaccines185
- IX. Tumor Antigens as Surrogate Markers and Targets for Therapy and Vaccines186
- X. Summary and Future Directions187
- References188
- Chapter 8: Practices and Pitfalls of Mouse Cancer Models in Drug Discovery191
- I. Why Are Animal Models Needed?191
- II. Model Types: Tumor Locations193
- III. Tumor Models: Cell Types198
- IV. Study Endpoints199
- V. Animal Modeling in the Post-genomics Age203
- VI. Conclusions207
- References207
- Chapter 9: Pharmacodynamic Biomarkers for Molecular Cancer Therapeutics213
- I. Introduction214
- II. Types of Biomarkers216
- III. The Pharmacological Audit Trail218
- IV. Methodological Issues220
- V. Rationale for Use of PD Markers to Facilitate Drug Development222
- VI. The Need for Multidisciplinary and Broad-Based Collaborative Research and Development229
- VII. Biomarker Methodology230
- VIII. Examples of PD Biomarkers for Specific New Drug Classes237
- IX. Combining Chemotherapy with Molecularly Targeted Agents252
- X. Conclusions and Future Perspective253
- Acknowledgments255
- References255
- Chapter 10: Biomarker Assay Translation from Discovery to Clinical Studies In Cancer Drug Developmen269
- I. Introduction270
- II. Biomarkers and Cancer Drug Development272
- III. Biomarker Research Challenges: Technology Translation275
- IV. Biomarker Research Challenges: Cultural and Process Translation281
- V. Clinical Qualification291
- VI. Conclusions and Perspectives294
- Acknowledgments296
- References296
- Chapter 11: Molecular Optical Imaging of Therapeutic Targets of Cancer299
- I. Introduction300
- II. Role of Molecular-Specific Optical Imaging of Carcinogenesis302
- III. Cancer Biomarkers and Therapeutic Targets304
- IV. Optical Technologies306
- V. Optically Active Contrast Agents311
- VI. Delivery of Contrast Agents In Vivo322
- VII. Molecular-Specific Optical Imaging324
- VIII. Future Directions: "Smart" Contrast Agents331
- IX. Conclusions335
- References336
- Chapter 12: Personalized Medicine for Cancer: From Molecular Signature to Therapeutic Choice345
- I. Summary345
- II. Introduction346
- III. Prevention and Screening351
- IV. Detecting Cancer353
- V. New Treatment Approaches354
- VI. The Development of Personalized Medicine357
- VII. Barriers to Innovation361
- VIII. Patient's Experience363
- IX. Conclusions365
- References369
- Chapter 13: Cancer Drug Approval in the United States, Europe, and Japan371
- I. USA371
- II. Europe381
- III. Japan384
- IV. Discussion387
- Index393
The Advances in Cancer Research series provides invaluable information on the exciting and fast-moving field of cancer research. This volume stands as the first ever thematic volume in the series, focusing on the topic of genomics in cancer drug development. The chapters included in this book represent the cutting-edge information in the field and span such topics as Mass Spectrometry: Uncovering the Cancer Proteome for Diagnostics; Biomarker Discovery in Epithelial Ovarian Cancer by Genomic Approaches; The Application of siRNA Technology to Cancer Biology Discovery; Ribozyme Technology for Cancer Gene Target Identification and Validation; Cancer Cell-Based Genomic and Small Molecule Screens; Tumour Antigens as Surrogate Markers and Targets for Therapy and Vaccines; Practices and Pitfalls of Mouse Cancer Models in Drug Discovery; Biomarker Assay Translation from Discovery to Clinical Studies in Cancer Drug Development – Quantification of Emerging Protein Biomarkers; Molecular Optical Imaging of Therapeutic Targets of Cancer; Cancer Drug Approval in the United States, Europe and Japan.