Chapter
1. Cancer as a Genetic Disease
1.1. The Genetic Basis of Cancer
-Cancer Epigenetics
1.2. Cancer Statistics: Mortality Has Decreased, but the Number of
New Cases Is Increasing
Cancer Survivor Care
1.3. What Are Molecularly Targeted Drugs?
1.4. Target Selection versus Patient Selection
1.5. The Future of Cancer Care
-Parallels between Human Immunodeficiency Virus/Acquired Immunodeficiency
Syndrome and Cancer Care
1.6. The Diagnostic Potential of Druggable Targets
Chapter 2. Targeted Therapies: Early Success Stories and Promising
Candidates
2.1. Small Molecule Drugs
-Gleevec (Imatinib): Approved 2001
-Iressa (Gefitinib): Approved May 2003
-Tarceva (Erlotinib): Approved November 2004
-Promising Small Molecule Drugs in Development
2.2. Hypomethylating Agents
-Azacitidine
-Decitabine and Zebularine
2.3. Immunotherapeutic Intervention: Antibodies and Vaccines
-Therapeutic Monoclonal Antibodies
-Rituxan (Rituximab)
-Herceptin (Trastuzumab)
-Immunoconjugates
-Avastin (Bevacizumab)
-Cancer Vaccines
Chapter 3. Toward Targeted Therapies: Preclinical Discovery Technology
3.1. Finding the Cancer Gene: Discovery Technology
-Comparative Genomic Hybridization (CGH)
-Array CGH
3.2. The Human Genome Project
-Advances in Sequencing Technology: Digital Karyotyping as an Example
-Accelerated Drug Discovery
3.3. Oncogenomic Diagnostic Testing: Gene Expression Technology
-Transcription Profiling Technology
-Oncogenomics Normal Tissue Database
3.4. Proteomics and Cancer Care
3.5. Preclinical Validation: Screening Cancer Genes
Chapter 4. Patient-Selected Targeted Drugs in the Clinic: Opportunities
and Challenges
4.1. The Gleevec Paradigm: From Skepticism to Iressa
4.2. The Importance of Patient Selection: A Scientific Argument
4.3. The Small-Size Advantage of Patient-Selected Trials
4.4. How to Design Patient-Selected Clinical Trials
4.5. Sample Acquisition as a Major Barrier to Patient-Selected
Research
4.6. Lessons about Sample Acquisition from Past Attempts to Individualize
Cancer Chemotherapy
4.7. Patient Selection from the Patient, Physician, and Payer Perspective:
Disincentives
Chapter 5. The Business of Oncogenomics: Challenges and Opportunities
5.1. Public and Academic Involvement in Translational Research
-Drug Discovery
5.2. The Potential Financial Rewards of a Patient-Selected Tiered
Market
-Expanding Indications for Targeted Drugs
-Drug Safety
-The Scientific Counterargument
5.3. The Molecular Diagnostics Industry
-Patient-Selected Molecular Diagnostics
Chapter 6. Expert Interviews
Charles Brenner, PhD, Dartmouth Medical School; Coeditor (with
David Duggan), Oncogenomics: Molecular Approaches to Cancer
Walter P. Carney, PhD, Oncogene Science (part of Bayer HealthCare)
Nicholas C. Dracopoli, PhD, Vice President of Clinical Discovery
Technology, Pharmaceutical Research Institute, Bristol-Myers Squibb
Geoffrey Duyk, MD, PhD, Managing Director, Texas Pacific Group
Ventures
Michael L. Salgaller, PhD, Toucan Capital Corporation
Herman Spolders, PhD, Chief Executive Officer, OncoMethylome Sciences
Chapter 7. Company Profiles
Abgenix, Inc.
ArtisOptimus, Inc.
Dendreon Corporation
Genomic Health, Inc.
ImClone Systems, Inc.
Medarex, Inc.
OncoMethylome Sciences, Inc.
Onyx Pharmaceuticals, Inc.
OSI Pharmaceuticals, Inc.
Spectral Genomics, Inc.
Vivo Biosciences, Inc.
Notes
Glossary
Index
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