Biomarker Methods in Drug Discovery and Development

The pharmaceutical industry has faced many significant challenges since the early 1990s. The fundamental issue that needs to be addressed is how to improve the efficiency of drug discovery and development. The current research and development (R&D) cost for developing a new therapeutic drug is greater than $800 million. Additionally, it takes an average of 12 years to get a new drug to market with an attrition rate greater than 90%. Reviewing the overall pharmaceutical R&D process, it has become clear that many of the drug failures are due to our lack of knowledge in population diversity, which is responsible for differences in drug efficacy and toxicity. In fact, not a single approved drug is 100% safe and efficacious for all patients. For researchers, the key question is: How can we discover biomarkers that can be used to distinguish patients who will respond to the drug without adverse effects from those who will not respond and/or will have adverse effects? There is tremendous urgency to address this question. Biomarkers also fit perfectly with the vision of personalized medicine, the new expectation of medical practice. This is why biomarker research has been a central focus in many research labs across academia, government agencies, and the pharmaceutical industry. There are many different ways to define biomarkers based on molecular properties, applications, and methods.

Table of Content Preface Contributors Chapter 1 Biomarker sample collection and handling in the clinical setting to support early phase drug development Chris B. Russell, Sid Suggs, Kristina M. Robson, Keith Kerkof, Lisa D. Kivman, Kimberly H. Notari, William A. Rees, Natalia Leshinsky, and Scott D. Patterson Chapter 2 Gene Expression-Based Biomarkers of Drug Safety Eric A.G. Blomme, and Scott E. Warder Chapter 3 Profiling Gene Expression Signatures Using Fluorescent Microspheres Suzanne M. Torontali, Jorge M. Naciff, Kenton D. Juhlin, and Jay P. Tiesman Chapter 4 Real-Time PCR Gene Expression Assays in Biomarker Discovery and Validation Yulei Wang, Catalin Barbacioru, David Keys, Pius Brzoska, Caifu Chen, Kelly Li, and Raymond R. Samaha Chapter 5 SAGE Analysis in Identifying Phenotype SNPs Sandro J. de Souza, I-Mei Siu, Janete M. Cerutti, and Gregory J. Riggins Chapter 6 SNP and DNA Methylation Analysis using Pyrosequencing Methods Jinsheng Yu, and Sharon Marsh Chapter 7 The Application of LCM for the Analysis of Specific Cell-Type Gene Expression in a Complex Tissue: the Primate Endometrium William C. Okulicz Chapter 8 The use of Two-Dimensional Gel Electrophoresis for Plasma Biomarker Discovery Brad Jarrold, Alex Varbanov, and Feng Wang Chapter 9 Difference In Gel Electrophoresis (DIGE), a high resolution protein biomarker research tool David S. Gibson, David Bramwell, and Caitriona Scaife Chapter 10 Label-free Mass Spectrometry-based Protein Quantification Technologies in Protein Biomarker Discovery Mu Wang, Jin-Sam You, Kerry G. Bemis, and Dawn P. G. Fitzpatrick Chapter 11 Top-Down Quantitative Proteomic Analysis using a Highly Multiplexed Isobaric Mass Tagging Strategy Bing Xie, Wayne F. Patton, and Craig E. Parman Chapter 12 SELDI Technology for Identification of Protein Biomarkers Prasad Devarajan, and Gary F. Ross Chapter 13 Sandwich ELISA Microarrays: Generating Reliable and Reproducible Assays for High Throughput Screens Rachel M Gonzalez, Susan M Varnum, and Richard C Zangar Chapter 14 LC-MS Metabonomics Methodology in Biomarker Discovery Xin Lu, and Guowang Xu Chapter 15 GC/MS–based metabolomics Sally-Ann Fancy, and Klaus Rumpel Chapter16 NMR-Based Metabolomics for Biomarker Discovery Narasimhamurthy Shanaiah, Shucha Zhang, M. Aruni Desilva, and Daniel Raftery Chapter 17 Unraveling Glycerophospholipidomes by Lipidomics Kim Ekroos Index