Emerging Targets in Diseases with High Unmet Need: Alzheimer's Disease, Lung Cancer, Dyslipidemia, Type 2 Diabetes and COPD

Table of Contents

Chapter 1. Background: Targets and Target-Based Drug Discovery and Development

• 1.1. What Is a Drug Target?
• 1.2. The Target Validation Problem
• Sidebar: Q&A with Dr. Neil W. Gibson, Chief Scientific Officer of OSI Pharmaceuticals, on Target Validation
• 1.3. Target Validation and Falling Productivity of Pharmaceutical Research and Development
• 1.4. A More Realistic View of Target Validation
• 1.5. Approaches to Improving the Productivity of Target Evaluation and of Drug Discovery
• Dealing with Multiple Molecular "Causes" of Disease by Hitting More than One Target
• Whole-Pathway Approaches
• Biology-Driven Drug Discovery
• 1.6. Special Issues with Complex Diseases with High Unmet Medical Need
• Biomarkers, Targets, and Patient Stratification
• Animal Models and Complex Diseases

Chapter 2. Alzheimer's Disease

• 2.1. Pathobiology and Mechanistic Studies of Alzheimer's Disease
• Neurotransmitters and Alzheimer's Drugs
• The Amyloid Hypothesis
• Apolipoprotein E and Alzheimer's Disease
• Mechanistic Studies of Tau and Alpha Synuclein in Alzheimer's Disease
• 2.2. Prospects for Biomarkers in Detection of Presymptomatic and Early-Stage Alzheimer's Disease and in Monitoring Therapy
• 2.3. Selected Emerging Targets in Alzheimer's Disease
• Neural Nicotinic Receptors
• Beta-Amyloid
• Beta-Secretase and Gamma-Secretase
• Sidebar: Q&A with Dr. Adrian N. Hobden, President of Myriad Pharmaceuticals, Inc., on the Challenges of Developing the Novel-Acting Agent Flurizan for Alzheimer's Disease
• Somatostatin Receptors and Metabolism of Beta-Amyloid
• The Tau Pathway
• Apolipoprotein E
• 2.4. Outlook

Chapter 3. Lung Cancer

• 3.1. Types of Lung Cancer
• 3.2. Current Diagnosis of Lung Cancer
• 3.3. Current Therapies for Lung Cancer
• 3.4. Signaling Pathways and Strategies for Targeted Therapies in Non-Small-Cell Lung Cancer
• 3.5. Selected Emerging Targets in Lung Cancer
• Epidermal Growth Factor Receptor
• K-Ras
• B-Raf
• Mitogen-Activated Protein Kinase Kinase
• Vascular Endothelial Growth Factor Receptor
• Aromatose
• Hedgehog Signaling Pathway
• 3.6. Outlook

Chapter 4. Dyslipidemia

• 4.1. Statins: Their Benefits and Their Limitations
• 4.2. Mechanistic Issues in Atherogenic Dyslipidemia
• Anti-Atherogenic Effects of High-Density Lipoprotein
• Metabolic Syndrome, High-Density Lipoprotein, and Triglycerides
• 4.3. Selected Emerging Targets in Dyslipidemia
• Cholesteryl Ester Transfer Protein
• Targeting High-Density Lipoprotein with Mimetics
• Peroxisome Proliferator-Activated Receptors Alpha and Delta
• Liver X Receptor
• 4.4. Outlook

Chapter 5. Type 2 Diabetes

• 5.1. Current Therapies
• 5.2. Difficulties in Drug Discovery in Type 2 Diabetes
• 5.3. Selected Emerging Targets in Type 2 Diabetes
• Dipeptidyl Peptidase-IV
• Simultaneous Targeting of PPAR-Alpha and PPAR-Beta
• Cannabinoid-1 Receptor
• S6 Kinase 1
• 11 Beta-Hydroxysteroid Dehydrogenase Type 1
• Recombinant Adiponectin
• Matrix Metalloproteinases
• 5.4. Outlook

Chapter 6. Chronic Obstructive Pulmonary Disease

• 6.1. Introduction
• Chronic Bronchitis
• Emphysema
• 6.2. Current Treatments
• 6.3. Animal Models in COPD
• 6.4. Selected Emerging Targets for COPD
• Proteinases (Matrix Metalloproteinases and Neutrophil Elastase)
• Phosphodiesterase-4
• Oxidant/Antioxidant Balance
• Leukotriene B4
• CXC Chemokines
• Tumor Necrosis Factor-Alpha
• 6.5. Outlook

Chapter 7. General Conclusions

• 7.1. Biology-Driven versus Technology-Driven Drug Discovery
• 7.2. Multitargeted Drugs and Combination Therapies
• 7.3. Biomarkers, Diagnostics, and Disease Stratification

Chapter 8. Company Profiles

• 8.1. Alzheimer's Disease
• Axonyx
• Elan
• Myriad Genetics
• Neurochem
• Targacept
• 8.2. Lung Cancer
• AstraZeneca
• Curis
• Genentech
• Onyx Pharmaceuticals
• OSI Pharmaceuticals
• Pfizer
• Wyeth
• 8.3. Dyslipidemia
• Avant Immunotherapeutics, Inc.
• Exelixis
• GlaxoSmithKline
• Ligand Pharmaceuticals
• Pfizer
• 8.4. Type 2 Diabetes
• Biovitrum
• Bristol-Myers Squibb
• Merck
• Novartis
• sanofi-aventis
• 8.5. Chronic Obstructive Pulmonary Disease
• Aeolus Pharmaceuticals
• ALTANA Pharma
• Arriva
• Dompe
• Pfizer

References

Glossary

Company Index with Web Sites