(PDF) Novel Anticancer Agents By Alex A. Adjei

This is the PDF eBook version for Novel Anticancer Agents – Strategies for Discovery and Clinical Testing By Alex A. Adjei, John K. Buolamwini

Table of Contents

Preface
Part I: Strategies for Drug Discovery
Chapter 1. A Survey of Novel Molecular Targets for Anticancer Drug Discovery
I. Introduction
II. Overview of Growth Factor Induced Mitogenic Signaling
III. Protein Kinases and Phosphatases
IV. Adapter Proteins
V. GTP-Binding Proteins
VI. Oncogenic Transcription Factors
VII. Apoptosis, Cell Survival, and Life Span Targets
VIII. Angiogenesis and Metastasis Molecular Factors
IX. Protein Degradation and Chaperoning Targets
X. Chromatin Remodeling Factors
XI. Conclusion
References
Chapter 2. Microarrays: Small Spots Produce Major Advances in Pharmacogenomics
I. Introduction to Microarrays
II. Advantages of DNA Microarrays
III. Major DNA Array Formats: Something for Everyone
IV. What is the Best Way to Interface with Microarrays?
V. Microarrays and Pharmacogenomics: Revolutionizing Discovery of New Drugs and Gene Function
VI. What Can Go Wrong in cDNA Microarray Experimentation?
VII. Array-Based Proteomics: How to Investigate Protein Complexity
VIII. Emerging Microarray Technologies for High-Throughput Proteome Investigation: A Technical Overv
IX. Current and Future Applications of Protein Arrays in Drug Discovery
X. How to Deal with all that Data
XI. The Future is Only Going to Get Better
References
Chapter 3. Strategies to Target Chemotherapeutics to Tumors
I. Background and Rationale
II. Antibody-Directed Enzyme Prodrug Technique
III. Passive Tumor Targeting
IV. Targeting by Binding to Tumor Cell Surface Molecules
V. Enzyme-Activated Targeting
VI. Summary and Future Directions
References
Chapter 4. QSAR and Pharmacophore Mapping Strategies in Novel Anticancer Drug Discovery
I. Introduction
II. Pharmacophore Definition
III. Pharmacophore Validation
IV. Conclusions
References
Chapter 5. Applications of Nuclear Magnetic Resonance and Mass Spectrometry to Anticancer Drug Disco
I. Introduction
II. NMR in Anticancer Drug Discovery
III. Mass Spectrometry in Anticancer Drug Discovery
IV. MS/NMR Screening Assay
V. Conclusions
Acknowledgements
References
Chapter 6. Antisense Strategies for the Development of Novel Cancer Therapeutics
I. Introduction
II. Design and Evaluation of Antisence Oligonucleotides
III. Conclusion
Acknowledgements
References
Chapter 7. Antibodies and Vaccines as Novel Cancer Therapeutics
I. Introduction
II. Anti-Tumor Antibodies
III. Cancer Vaccines
IV. Conclusion
References
Chapter 8. Inhibitors of Apoptosis as Targets for Cancer Therapy
I. The Inhibitors of Apoptosis
II. Concluding Remarks
References
Chapter 9. Preclinical Testing and Validation of Novel Anticancer Agents
I. Introduction
II. Target Validation
III. A Generic Cascade for Anticancer Drug Discovery
IV. High-Throughput Cell-Free Screens for Activity Against the Target
V. In Vitro Cell Line Models
VI. In Vivo Testing of Novel Compounds
VII. Cassette-Dosing
VIII. Pharmaceutical Considerations
IX. High-Throughput In Vivo Anti-Tumor Testing: The Hollow Fiber Assay
X. Human Tumor Xenografts
XI. Orthotopic, Transgenic, and Other Animal Models
XII. Pharmacodynamics
XIII. Summary
Acknowledgements
References
Part II: Methods for Clinical Testing of Novel Agents
Chapter 10. Surrogate End Points and Biomarkers for Early Trials of Novel Anticancer Agents
I. Introduction
II. What are Targeted Agents?
III. Surrogate Markers or Biomarkers?
IV. Biomarkers as Indicators of Drug Effect In Vivo
V. Biomarkers as Predictive Factors
VI. Biomarkers as Prognostic Factors
VII. Technical Issues in the Evaluation of Drug Effects In Vivo
VIII. Lessons for the Future
Acknowledgements
References
Chapter 11. Regulatory Considerations in Clinical Trials of Novel Anticancer Drugs
I. Introduction
II. Overview of Cancer Drug Regulation
III. Regulatory Considerations in Early Cancer Drug Development
IV. Regulatory Considerations in Late Drug Development
V. Conclusion
Acknowledgements
References
Chapter 12. Improving the Efficacy and Safety of Anticancer Agents–The Role of Pharmacogenetics
I. Introduction
II. Thiopurine Methyltransferase
III. DPD
IV. Thymidylate Synthase
V. ABC Family of Drug Transporters
VI. UDP-Glucuronosyltransferase IAI Pharmacogenetics and Irinotecan
VII. MTHFR Reductase Pharmacogenetics
VIII. Cytochrome P4503A Pharmacogenetics
IX. Conclusion
Acknowledgements
References
Chapter 13. Imaging of Pharmacodynamic End Points in Clinical Trials
I. Introduction
II. PET
III. Evaluation of Cancer Therapeutics with PET
IV. MRI Assessment of Microvessel Function
V. Conclusions
References
Chapter 14. Devising Proof-of-Concept Strategies in Oncology Clinical Trials
I. Introduction
II. Proof-of-Concept
III. Elements of “The Concept”
IV. Application of Surrogate End Points in Proof-of-Concept Decision Making
V. Selected Statistical Considerations in Proof-of-Concept Studies
VI. Pharmacodynamic Proof-of-Concept End Points
VII. Pharmacokinetic Proof-of-Concept End Points
VIII. Proceeding From Proof-of-Concept Directly to Phase III
IX. Guidelines and Summary
Acknowledgements
References
Chapter 15. Clinical Trial Designs for Cytostatic Agents and Agents Directed at Novel Molecular Targ
I. Introduction
II. Phase I Dose-Finding Trials
III. Preliminary Efficacy Trials
IV. Definitive Randomized Efficacy Trials
V. Conclusions
References
Chapter 16. Cancer Gene Therapy Clinical Trials: From the Bench to the Clinic
I. Regulatory Requirements and Good Manufacturing Practices for Gene Transfer Products
II. Preclinical Development of Gene Therapy Vectors/Toxicology Testing
III. Federal and Institutional Approval Processes for Clinical Gene Therapy Trials
IV. Gene Therapy Clinical Trial Design
V. Correlative End Points
References
Chapter 17. Molecular Targets for Radiosensitization
I. Introduction
II. Growth Factor Receptors
III. Ras
IV. Modulation of p53
V. DNA Damage Recognition and Repair
VI. Other Promising Approaches
VII. Conclusions
VIII. Addendum
Addendum References
References
Chapter 18. Patient Accrual to Clinical Trials
I. Introduction
II. Setting Up the Environment
References
Index
Color Plate Section