Target Discovery and Validation Reviews and Protocols: Emerging Strategies for Targets and Biomarker Discovery, Volume 1 / Edition 1

by Mouldy Sioud

Overview

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.

Product Details

ISBN-13:	9781617376993
Publisher:	Springer-Verlag New York, LLC
Publication date:	11/19/2010
Series:	Methods in Molecular Biology , #360
Edition description:	Softcover reprint of hardcover 1st ed. 2007
Pages:	354
Product dimensions:	5.98(w) x 9.02(h) x 0.24(d)

Table of Contents

Main Approaches to Target Discovery and Validation.- Bioinformatics Approaches to Cancer Gene Discovery.- Analysis of Gene Networks for Drug Target Discovery and Validation.- Target Discovery and Validation in Pancreatic Cancer.- Molecular Classification of Breast Tumors.- Discovery of Differentially Expressed Genes.- Genome-Wide Screening by Using Small-Interfering RNA-Expression Libraries.- Hammerhead Ribozyme-Based Target Discovery.- Production of siRNA and cDNA-Transfected Cell Arrays on Noncoated Chambered Coverglass for High-Content Screening Microscopy in Living Cells.- Transgenic Animal Models in Biomedical Research.- Keratin Transgenic and Knockout Mice.- The HUVEC/Matrigel Assay.- A Murine Model for Studying Hematopoiesis and Immunity in Heart Failure.- An Overview of the Immune System and Technical Advances in Tumor Antigen Discovery and Validation.- Potential Target Antigens for Immunotherapy Identified by Serological Expression Cloning (SEREX).- Identification of Tumor Antigens by Using Proteomics.- Protein Arrays.

Editorial Reviews

From the reviews:

"Volume 1 focuses on novel and innovative techniques, and presents the most up-to-date prools 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 prools 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)

From the Publisher

Reviewer: Xiaobo Zhong, Ph.D.(University of Kansas Medical Center)
Description: This book in the Methods in Molecular Biology series presents the recent technological advances for the identification of molecular drug targets, biomarkers, and tumor antigens. It also describes the role of knockout mice in functional genomics and target validation, as well as the clinical impact of gene expression profiling on oncology diagnosis, prognosis, and treatment. Overviews and protocols are presented by experts in the fields.
Purpose: The purpose is to provide emerging strategies to identify and validate disease-causing target genes for drug discovery and development.
Audience: According to the editor, the topics will be of interest to researchers, pharmaceutical companies, and clinicians developing new drugs or using new therapies. In addition, this book will assist academic clinicians and students of biology, medicine, or pharmacy to appreciate the progress of the past few years in our understanding of cancer pathogenesis, cell signaling, gene profiling approaches, tumor immunology, tumor immunoediting, and immune tolerance.
Features: The 17 chapters include up-to-date overviews and protocols for drug target discovery and validation. Approaches include the use of small-interfering RNA-expression libraries, siRNA and cDNA-transfected cell arrays, hammerhead ribozyme-based target discovery, protein arrays, transgenic and knockout mice, and an in vivo HUVEC/Matrigel assay. As examples of human diseases, cancers (pancreatic and breast) and autoimmune disorders are discussed with respect to new drug discovery through application of the described strategies. Main concepts and approaches are summarized for readers to help them understand the recent technical advances.
Assessment: As a researcher in the field of pharmacogenomics, I think this is a very useful reference for drug target identification and validation. It covers almost all the recent technical advances in this area, which is an essential first step in drug discovery and development. These approaches will help us better understand the molecular mechanisms of many human diseases. Researchers and students in biology, medicine, and pharmacy should derive great benefit from reading this book.

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