Abstract:
Target Discovery and Validation Reviews and Protocols, Volumes 1 and 2 review the most progressive and current methods for drug target discovery and validation. These volumes explore how recent improvement in understanding the molecular mechanisms of human pathology is impacting drug target discovery in the laboratory and in real therapeutics, specifically for cancers and autoimmune disorders. Volume 1 focuses on novel and innovative techniques, and presents the most up-to-date protocols available for maximizing the likelihood of achieving target-selective inhibition in vivo while minimizing side effects. The profound impact of genomics, proteomics and bioinformatics on target discovery is explored, and specific attention is given to the role of transgenic and knockout animals in functional genomics and target validation. Cancer researchers will find tremendous value in the molecular classification of breast cancers and the review of protocols for tumor antigens and cancer vaccines. The methods and protocols collected here, all reviewed by leading scientists and clinicians, present the practical details necessary for translating the enormous discovery potential of the genome into real therapeutic products. Volume 2 collects all the practical details required for efficient translation of discovered targets into real pharmaceutical drugs. Specific targets in cancers and autoimmunity are described and the potential of using siRNAs, antisense oligonucleotides and RNA aptamers in patients is reviewed. This volume explores the tremendous impact of the application of genotyping and gene expression profiling on the future of healthcare, and presents cutting-edge protocols to aid in bringing agents against specific targets closer to application in the clinic. Collectively, these volumes provide a thorough review of the most cutting-edge methods available for each step in drug target identification, validation, and clinical application. For researchers, an understanding of available methods aids in the creation of innovative experiments in the laboratory, and the successful translation of target discovery to real therapeutics.
1. Druggable Signaling Proteins
Mouldy Sioud; Marianne Leirdal
pp. 1-24
2. DNA Methylation and Histone Modifications in Patients With Cancer: Potential Prognostic and Therapeutic Targets
Michel Herranz; Manel Esteller
pp. 25-62
3. Wnt Signaling as a Therapeutic Target for Cancer
Andreas Herbst; Frank Thomas Kolligs
pp. 63-92
4. NG2/HMP Proteoglycan as a Cancer Therapeutic Target
Martha Chekenya; Heike Immervoll
pp. 93-118
5. Heterotrimeric G Proteins and Disease
Øyvind Melien
pp. 119-144
6. High-Mobility Group Box-1 Isoforms as Potential Therapeutic Targets in Sepsis
William Parrish; Luis Ulloa
pp. 145-162
7. Antisense Oligonucleotides: Target Validation and Development of Systemically Delivered Therapeutic Nanoparticles
Chuanbo Zhang; Jin Pei; Deepak Kumar; Isamu Sakabe; Howard E. Boudreau; Prafulla C. Gokhale; Usha N. Kasid
pp. 163-186
8. Nucleic Acid-Based Aptamers as Promising Therapeutics in Neoplastic Diseases
Laura Cerchia; Vittorio de Franciscis
pp. 187-200
9. Guidelines for the Selection of Effective Short-Interfering RNA Sequences for Functional Genomics
Kumiko Ui-Tei; Yuki Naito; Kaoru Saigo
pp. 201-216
10. Suppression of Apoptosis in the Liver by Systemic and Local Delivery of Small-Interfering RNAs
Lars Zender; Stefan Kubicka
pp. 217-226
11. Target Validation Using RNA Interference in Solid Tumors
Seyedhossein Aharinejad; Mouldy Sioud; Trevor Lucas; Dietmar Abraham
pp. 227-238
12. Validation of Telomerase and Survivin as Anticancer Therapeutic Targets Using Ribozymes and Small-Interfering RNAs
Nadia Zaffaroni; Marzia Pennati; Marco Folini
pp. 239-264
13. Collagen-Induced Arthritis in Mice: A Major Role for Tumor Necrosis Factor-?
Richard O. Williams
pp. 265-284
14. Novel Opportunities for Therapeutic Targeting in Systemic Autoimmune Diseases
Meryem Ouarzane; Moncef Zouali
pp. 285-298
15. Considerations for Target Validation and Industrial Approaches
Carlos R. Plata-Salamán; Sergey E. Ilyin
pp. 299-310
16. Regulatory RNAs: Future Perspectives in Diagnosis, Prognosis, and Individualized Therapy
Marjorie P. Perron; Vincent Boissonneault; Lise-Andrée Gobeil; Dominique L. Ouellet; Patrick Provost
pp. 311-326
17. Treatment Options and Individualized Medicine
Mouldy Sioud; Øyvind Melien
pp. 327-340