The Impact of Genomics Clinical Trials and Medical Practice

Table of Contents

• Chapter 1. Introduction
  • 1.1. Overview
  • 1.2. The Impact of Genomics in the Clinic
    • Definition and Scope of Clinical Genomics
    • Preclinical Versus Clinical Applications of Genomics
  • 1.3. Impact of Data from the Human Genome
    • The Human Genome Project
    • Sidebar: Brief Timeline of Human Genomics
    • Peculiarities of the Human Genome
    • Advantages of a Genomics Approach
  • 1.4. The Promise of Clinical Genomics
    • Sidebar: Our Genomic Destiny: Fact or Fiction
    • Potential Impact on Medical Practice
    • -Personalized Medicine
    • -Toxicogenomics: Fewer Adverse Drug Reactions
    • -Predicting Disease
    • Sidebar: NHGRI's Vision for the Future of Genomics
    • -Improving Clinical Trials
    • -Predicting Response to Drugs
    • -Better Drug Design
  • 1.5. Challenges in the Field
    • Scientific Challenges
    • -Variation in Drug Response
    • -Disease Complexity
    • -Characterization of Genetic Variation
    • -Genome Complexity
    • Technological Challenges
    • -DNA Technologies
    • -Microarrays
    • -Regulatory Challenges
    • -The FDA
    • -Congress
    • Legal Challenges
    • -Intellectual Property
    • -Liability
    • Sidebar: The Biojudiciary Project
    • Economic Challenges
    • Sociological and Cultural Challenges
    • -Medical Education
    • -Patient Acceptance
    • -Ethical Considerations
• Chapter 2. Applications of Genomics in Clinical Trials and Medicine
  • 2.1. Prediction, Detection, and Diagnosis of Disease
  • 2.2. Predicting Response to Drugs
    • Historical Perspective
    • Pharmacogenomics
  • 2.3. Factors Influencing Response to Drugs
    • Drug Metabolism
    • -Pharmacogenomics of Phase I Drug Metabolism
    • -Pharmacogenetics of Phase II Drug Metabolism: N-Acetyltransferase
    • -Pharmacogenetics of Phase II Drug Metabolism: Thiopurine S-Methyltransferase
    • Drug Transporters
    • Genetic Polymorphism of Drug Targets
    • Genetic Variants with Indirect Effects on Drug Response
  • 2.4. Personalized Medicine
    • Variation in Gene Expression
    • Cancer Classification, Diagnosis, and Prognosis
    • -Cancer Classification
    • -Cancer Diagnosis
    • Sidebar: Cancer Genome Anatomy Project
    • -Cancer Prognosis
  • 2.5. Toxicogenomics
  • 2.6. Determining Risk of Disease
    • Inherited Genetic Variation
    • Sidebar: Categories of Inherited DNA Diseases
    • Single-Gene Genetic Disorders
    • -Monogenic Trait Example: Cystic Fibrosis
    • Multifactorial Disorders
    • -Multifactorial Disease Example #1: Alzheimer's Disease
    • -Multifactorial Disease Example #2: Cancer
    • Sidebar: Genetic Origin of Cancers
    • Screening Newborns
  • 2.7. Gene Therapy
  • 2.8. Identifying Individuals
    • Paternity Testing
    • Forensics
    • Identifying Remains
  • 2.9. Proteomics
• Chapter 3. Genomic Technologies for the Clinic
  • 3.1. Overview
  • 3.2. Detecting DNA Variation
    • Single Nucleotide Polymorphisms
    • Haplotypes
    • -HapMap Project
    • -Selected Companies Active in Haplotypes
  • 3.3. SNP Genotyping Methods
    • Sidebar: SNP Detection
    • Evaluating SNP Technologies for Clinical Applications
    • -Cost of SNP Genotyping
    • -Success Rates
    • -Accuracy
    • Throughput Considerations
    • Selected Companies Active in SNP Genotyping
    • -Sequenom
    • -Illumina
    • -Affymetrix
    • -PerkinElmer
    • -Third Wave Technologies
    • -Applied Biosystems Group
    • -Beckman Coulter
  • 3.4. Gene Expression Detection
    • Methods for Measuring Gene Expression
    • -DNA Microarrays
    • -DNA Synthesis
    • -DNA Deposition
    • Box Feature: Gene Expression Database
    • Computational Issues
    • Evaluating the Technologies
    • Cross-Platform Comparisons
    • Selected Companies Marketing Gene Expression Microarrays
    • -Affymetrix
    • -Agilent Technologies
    • -Applied Biosystems
    • -CombiMatrix
    • -Brinkmann Instruments
  • 3.5. RNA Interference
    • Selected Companies Active in RNAi Therapy
    • -Alnylam Pharmaceuticals
    • -Sirna Therapeutics
    • -Acuity Pharmaceuticals
  • 3.6. Other Technologies
    • Epigenetic Markers
    • -Sequenom's Approach
    • -Epigenomics' DNA Methylation Technique
    • Alternative Splicing
    • Proteomics
• Chapter 4. Advances in Clinical Genomics Applications
  • 4.1. Overview
  • 4.2. Toxicogenomics
    • Adoption of Clinical Toxicogenomics Tests
    • Case Study #1: First Microarray Approved for Treatment Decisions
    • Sidebar: P450 Drug Interaction Card
    • Case Study #2: First Pharmacogenetic Test Approved As Companion to Therapy
    • Case Study #3: TPMT
  • 4.3. Clinical Trials
  • 4.4. Clinical Oncology
    • Case Study #1: Cancer Gene Expression
    • -Agendia's MammaPrint Gene Expression Assay
    • -Genomic Health's Oncotype DX
    • Case Study #2: Genentech's Herceptin and Her-2
    • Case Study #3: BRCA1 and BRCA2 Genes and Myriad Genetics
    • Box Feature 4.1: Human Cancer Genome Project
  • 4.5. Infectious Diseases
    • Case Study: HIV and AIDS
    • Other Applications for Genomics to Infectious Diseases
  • 4.6. Newborn Screening
  • 4.7. Genomics and Race
    • BiDil: The First Race-Based Drug
  • 4.8. Genomics and Drug Labeling
• Chapter 5. Business and Strategic Factors
  • 5.1. Overview
  • 5.2. Patient Stratification
    • Impact on Clinical Trials
    • Impact on the Market
  • 5.3. Scientific Issues
    • Can Clinical Genomics Deliver on Its Promise?
    • Can the Influence of Genes on Drug Response Be Quantified?
  • 5.4. Standardization and Quality Control
  • 5.5. Physician and Payer Response
  • 5.6. Drug-Diagnostic Codevelopment: Theranostics
  • 5.7. The Regulatory Environment
    • FDA Guidelines on Pharmacogenomics
    • "Home-Brew" Testing, In Vitro Diagnostics, and the FDA
  • 5.8. Cost-Benefit Analysis
    • Evaluating the Cost of Clinical Genomics
    • Factors Influencing Costs
    • Comparing Genomics With Other Testing and Treatment Options
    • Noteworthy Indications
  • 5.9. Niche Markets for Clinical Genomics
    • Opportunity in Rare Diseases
    • Outlook for Toxicogenomics
    • Projected RNAi Market
• Chapter 6. Expert Interviews
  • Edward Abrahams, PhD, Executive Director, Personalized Medicine Coalition (PMC)
  • Charles R. Cantor, PhD, Chief Scientific Officer SEQUENOM
  • Mickie Henshall, Product Manager, Molecular Diagnostics, Illumina, Inc.
  • William Craumer, Director, Corporate and Marketing Communications, Illumina, Inc.
  • Mark A. McCamish, MD, PhD, Chief Medical Officer, Perlegen Sciences
• Chapter 7. Selected Company Profiles
  • Affymetrix
  • Agendia
  • Alnylam Pharmaceuticals
  • Applied Biosystems Group (ABI)
  • Agilent
  • Beckman Coulter, Inc.
  • Brinkmann Instruments (A Member of the Eppendorf Group)
  • CombiMatrix Corporation
  • DnaPrint Genomics Inc.
  • Encode (Subsidiary of deCODE)6
  • Epigenomics AG
  • ExonHit Therapeutics
  • Genaissance Pharmaceuticals
  • Gene Logic
  • Genomic Health
  • Genpathway Inc.
  • Gentris
  • Iconix Pharmaceuticals, Inc.
  • Illumina
  • Invitrogen
  • Myriad Genetics
  • Nanogen
  • NitroMed, Inc.
  • PathWork Informatics
  • Perlegen Sciences
  • PTC Therapeutics, Inc.
  • Roche Molecular Diagnostics
  • SEQUENOM, Inc.
  • Sirna Therapeutics
  • Third Wave Technologies, Inc.
  • Vanda Pharmaceuticals
  • References
  • Index