Target discovery is a field that has existed for several years but is so vibrant today because of the recent progress in our understanding of the molecular mechanisms of many human diseases and the technical advances in target identification and validation. More sophisticated gene profiling technologies, such as DNA microarrays and serial analysis of gene expression, permit rapid identification of lead targets. Moreover, analysis of gene networks in living organisms allows the identification of target genes that operate in defined physiological pathways. With the sequencing of several genomes completed and the rapidly growing gene expression databases, there is now greater impetus than ever before for in silico discovery of therapeutic targets. Also, recent advances in genetic technologies have increased our ability to generate mouse models for human diseases. The implications of these genetically modified animals in drug development are several, including identification of new drug targets, predicting efficacy, and uncovering possible side effects. Together, these recent technical advances should allow researchers to make the most informed choice early and advance the chosen targets toward clinical studies. Regarding cancers, any difference between a cancer and a normal cell could potentially be exploited as a therapeutic target. The hope is that drugs targeting specific constituents or pathways in cancer cells will provide more effective therapy, either alone or in combination with other currently used anticancer drugs. In addition to drug targets, identifying new target antigens remains as much of a challenge as improving tumor vaccines already in the clinic.
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From the reviews:
"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. ... Cancer researchers will find tremendous value in the molecular classification of breast cancers and the review of protocols for tumor antigens and cancer vaccines. ... provide a thorough review of the most cutting-edge methods available for each step in drug target identification, validation, and clinical application." (Anticancer Research, Vol. 27, May, 2007)
"Review current methods for drug target discovery and validation. ... Volume 1 is focused on drug target and biomarker discovery. ... the chapters are generally well written and clear, and provide extensive references to the current literature. ... Overall ... provide useful overviews that would provide entry into this field. Novice and more experienced researchers ... would find useful information ... ." (Jonathan B. Chaires, ChemMedChem, Issue 3, 2008)
Target Discovery and Validation: Reviews and Protocols Part I: Emerging strategies for targets and biomarker discovery 1. Main approaches to target discovery and validation Mouldy Sioud 2. Bioinformatics approaches to cancer gene discovery Ramaswamy Narayanan 3. Analysis of gene networks for drug target discovery and validation Seiya Imoto, Yoshinori Tamada, Christopher J. Savoie, and Satoru Miyano 4. Target discovery and validation in pancreatic cancer Robert M. Beaty, Mads Gronborg, Jonathan R. Pollack, and Anirban Maitra 5. Molecular classification of breast tumors: Clinical impact on diagnosis, prognosis, and treatment Therese Sørlie 6. Discovery of differentially expressed genes: Technical considerations Øystein Røsok and Mouldy Sioud 7. Genome-wide screening using siRNA-expression libraries Sahohime Matsumoto, Makoto Miyagishi, Ryozo Nagai, and Kazunari Taira 8. Hammerhead ribozyme-based target discovery Masayuki Sano and Kazunari Taira 9. Production of siRNA and cDNA transfected cell arrays on non-coated chambered coverglass for high content screening microscopy in living cells Holger Erfle and Rainer Pepperkok 10. Transgenic animal models in biomedical research Louise-Marie Houdebine 11. Keratin transgenic and knockout mice: Functional analysis and validation of disease-causing mutations Preethi Vijayaraj, Goran Söhl, and Thomas M. Magin 12. The HUVEC/Matrigel assay - an in vivo assay of human angiogenesis suitable for drug validation Dag K. Skovseth, Axel M. Küchler, and Guttorm Haraldsen 13. A murine model for studying hematopoiesis and immunity in heart failure Per Ole Iversen and Dag R. Sørensen 14. An overview of the immune system and technical advances in tumor antigen discovery Mouldy Sioud 15. Potential target antigens for immunotherapy identified by serological expression cloning(SEREX) Dirk Jäger 16. Identification of tumor antigens using proteomics Françoise Le Naour 17. Protein arrays: a versatile toolbox for target identification and monitoring of patient immune responses Lina Cekaite, Eivind Hovig and Mouldy Sioud 18. Considerations for target validation and industrial approaches Carlos R. Plata-Salamán, and Sergey E. Ilyin
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