Drug Discovery in Pancreatic Cancer: Models and Techniques

ISBN-13: 9781441911599 / Angielski / Twarda / 2010 / 297 str.

Haiyong Han

Opis

Pancreatic cancer is the fourth leading cause of cancer death in the United States. Every year, about 33,700 people in the United States will be diagnosed with pancreatic cancer and over 32,000 patients will die from the disease. The median survival of patients with advanced pancreatic cancer is about 6-months. This dismal picture of pancreatic cancer is mainly due to the lack of early diagnosis and effective treatment for patients with advanced disease. To increase the survival rate of pancreatic cancer patients, better tumor markers for diagnosis and new molecular targets for drug development are desperately needed. A lot of effort has been made in searching for pancreatic cancer-causing genes or genes associated with progression of malignant behavior in pancreatic cancer. As a result, alterations in the expression of several cancer-related genes have been identified in pancreatic tumors. The identification and characterization of these cancer-related genes have significantly increased our understanding of pancreatic cancer development, but unfortunately the treatment of pancreatic cancer has not advanced as much in the past 20 years. Over the past decade, tremendous advances have been made in the field of cancer drug discovery, particularly, in the area of molecular and genetic models and technologies. Many of those advanced models and technologies have been applied to the drug discovery processes for pancreatic cancer. In this book, a team of experts will describe the latest development in the application of these models and technologies in pancreatic cancer. The authors include basic researchers as well as clinicians who work in the front-line of the war against pancreatic cancer and have the first-hand experience on these cutting-edge tools and techniques. The book can be divided into two general areas: 1) model systems and 2) genomics and proteomics tools. In recent years there have been a lot of advances in the model systems for pancreatic cancer, including the further characterization of normal and cancerous pancreatic cell lines, the establishment of transgenic mouse models that recapitulate the initiation and progression of human pancreatic cancer, the development of a new xenograft model system for the evaluation of novel agents, and the establishment of a zebrafish pancreatic cancer model. The first four chapters of the book will be devoted to these models. The advances in genomics and proteomics research have made a major impact in cancer drug discovery. A number of these omics-based tools and techniques have been applied in the pancreatic cancer drug discovery. Chapters 5-9 of the book will discuss techniques for genome-wide examination of gene expression, copy number, methylation, function and regulation. Chapters 10-11 will discuss in situ techniques for studying chromosomal and gene copy number abnormalities as well protein expression changes in cancer samples. Chapters 12-14 will focus on techniques for global examination of protein expression levels in biospecimens obtained from pancreatic cancer patients. Cancer drug discovery has become more and more target-centric. "

Spis treści

Chapter 1: Pancreatic cancer cell line models Steven Warner, Ph.D. Translational Genomics Research Institute Division of Clinical Translational Research Chapter 2: Pancreatic cancer xenograft models Manuel Hidalgo, M.D., Ph.D. Johns Hopkins University School of Medicine Chapter 3: Pancreatic cancer transgenic mouse models David A. Tuveson M.D., Ph.D. Cancer Research UK Cambridge Research Institute Chapter 4: Pancreatic cancer zebra fish models Steven Leach, M.D. Division of Surgical Oncology Johns Hopkins University School of Medicine Chapter 5: DNA microarray expression profiling Charles Gawad, M.D. School of Medicine University of California at Los Angeles Chapter 6: Array CGH profiling Robert Lucito, Ph.D. Cold Spring Harbor Laboratory Chapter 7: High throughput siRNA Spyro Mousses, Ph.D. Division of Pharmaceutical Genomics Translational Genomics Research Institute Chapter 8: miRNA profiling Glen J. Weiss, M.D University of Colorado Health Science Center Department of Hematology and Medical Oncology Chapter 9: Methylation detection and epigenetics Bernard W. Futscher, Ph.D. Arizona Cancer Center Chapter 10: Tissue microarray based IHC and FISH Anirban Maitra, MBBS The Sol Goldman Pancreatic Cancer Research Center Johns Hopkins University School of Medicine Chapter 11: Spectral Karyotyping (SKY) and M-FISH Thomas R. Dennis, Ph.D. Translational Genomics Research Institute Chapter 12: Proteomics analysis of serum and pancreatic juice Michael Goggins, M.D. The Sol Goldman Pancreatic Cancer Research Center The Johns Hopkins University School of Medicine Chapter 13: Glycomics analysis of serum and pancreatic juice samples J. Michael Pierce, Ph.D. University of Georgia Director, UGA Cancer Center Chapter 14: Protein arrays for pancreatic cancer research Raoul Tibes, M.D. Division of Pharmaceutical Genomics Translational Genomics Research Institute Chapter 15: Vaccines for pancreatic cancer Dan A. Laheru, M.D. Buntings Blaustein Cancer Research Building Room G89 Chapter 16: Molecular imaging of small animals Robert J. Gillies, Ph.D. Department of Radiology Arizona Cancer Center, MRB 138 Chapter 17 : Development of pharmacodynamic endpoint models for the evaluation of clinical activities of targeted therapeutics Amanda Baker, Ph.D. Arizona Cancer Center

Blurb

Over the past two decades, tremendous advances have been made in the field of cancer drug discovery, particularly in the area of molecular and genetic models and technologies, many of which have been or are beginning to be applied to the drug discovery process for pancreatic cancer. Drug Discovery in Pancreatic Cancer: Models and Techniques offers the latest development in the application of those models and technologies in pancreatic cancer. The authors include experts in their perspective field of research including basic scientists as well as clinicians who work on the frontline in the war against pancreatic cancer and have first-hand experience employing these cutting-edge tools and techniques. The book progresses logically from modeling systems to genomic profiling, proteomic analysis, and pharmacodynamic assays. It features: • Up-to-date survey of many cell lines and animal models of pancreatic cancer and their applications in drug discovery. • Application of fluorescent mouse models in pancreatic cancer drug discovery. • Utility of cutting-edge genomics, proteomics, epigenomics, and glycomics methodologies for molecular target identification and validation. • Discussion of microRNA profiling and high throughput RNAi screening for pancreatic cancer drug discovery. • Broad screening technologies for proteins and nucleic acids using tissue microarrays and CGH arrays. • Development of pharmacodynamic endpoint assays for targeted therapeutics. Comprehensive and practical Drug Discovery in Pancreatic Cancer: Models and Techniques offers both basic and clinical scientists who are interested in pancreatic cancer an up-to-date review and assessment of models and technologies being applied in drug discovery for pancreatic cancer. The true premise of this book is to provide a guide for drug discovery and evaluation, with consideration of various modeling systems and the methods for screening/profiling responses to these compounds. It is the Editors intent to stimulate new thought in this area of research as a means of generating much improved drug efficacy for greater survival and quality of life for patients battling pancreatic cancer.