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Textbook of Personalized Medicine Textbook of Personalized Medicine Textbook of Personalized Medicine Second Edition Kewal K. Jain, MD, FRACS, FFPM Jain PharmaBiotech, Basel, Switzerland Kewal K. Jain Jain PharmaBiotech Basel , Switzerland ISBN 978-1-4939-2552-0 ISBN 978-1-4939-2553-7 (eBook) DOI 10.1007/978-1-4939-2553-7 Library of Congress Control Number: 2015934582 Springer New York Heidelberg Dordrecht London © Springer Science+Business Media New York 2014, 2015 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper Humana Press is a brand of Springer Springer Science+Business Media LLC New York is part of Springer Science+Business Media (www.springer.com) “Tonight, I’m launching a new Precision Medicine Initiative to bring us closer to curing diseases like cancer and diabetes — and to give all of us access to the personalized information we need to keep ourselves and our families healthier.” —President Barack Obama, State of the Union Address, 20 January 2015, USA Preface to the Second Edition Considerable advances have taken place in technologies used for advancing person- alized medicine, and it is increasingly applied in clinical use. This has required expansion and revision of some parts of the fi rst edition published in 2009. The style has been maintained due to the positive feedback of readers, including scientists, pharmacists, physicians, and lay persons interested in this topic. The book provides a concise and comprehensive source of reference for those involved in healthcare management, planning, and politics. As a single author book, it avoids the overlaps and missing areas frequently found in multiauthor books. Moreover, the time to publication is reduced by avoiding the long delays of numerous authors who do not keep the deadlines. The book includes 700 references selected from thousands of publications during the past decade and appended at the end of each chapter. Some of the references included were prepublication versions at the end of 2014 that will not be formally published until 2015. The text is supplemented by 31 illustrations and 56 tables. Algorithms are included as a guide to those involved in the management of important diseases where decision making is involved due to the multiple choices available. Finally, I thank the editorial staff of Springer, particularly Patrick Marton and David Casey, for their help and encouragement in this project. Basel, Switzerland Kewal K. Jain vii Preface to the First Edition Personalized medicine, which simply means selection of treatment best suited for an individual, involves integration and translation of several new technologies in clinical care of patients. The scope is much broader than indicated by the term genomic medicine, because many non-genomic factors are taken into consideration in developing personalized medicine. Basic technologies for personalized medicine, of which molecular diagnostics has the biggest share, are mentioned briefl y and appropriate references are given for further information. Commercial aspects are discussed briefl y in a chapter and detailed analysis of markets and companies involved in personalized medicine is presented in a special report on this topic. There is increasing interest in personalized medicine. Considerable advances have taken place in molecular biology and biotechnology to make personalized medicine a viable option, but some misconceptions still exist, both in the academic and in the commercial sectors. There is lack of a suitable source of information that provides both the fundamentals as well as applications of personalized medicine. As the lat- est version of the fi rst monograph on personalized medicine published in 1998, this volume, Textbook of Personalized Medicine , summarizes the author’s efforts during the past decade as well as reviews of selected studies done during this period in a readable format for physicians and scientists. It is hoped that physicians, pharma- cists, scientists, and interested lay readers with basic scientifi c knowledge will fi nd this book useful. Basel, Switzerland Kewal K. Jain ix About the Author Professor K. K. Jain is a neurologist/neurosurgeon by training and has been work- ing in the biotechnology/biopharmaceuticals industry for several years. He received graduate training in both Europe and USA, has held academic positions in several countries, and is a Fellow of the Faculty of Pharmaceutical Medicine of the Royal College of Physicians of UK. Currently, he is a consultant at Jain PharmaBiotech. He has been working on developing personalized therapy by integrating new tech- nologies in addition to genomics since 1997. His monograph with the title Personalized Medicine published in 1998 was the fi rst treatise on this topic. Over the years, it went through several editions until it evolved into the Textbook of Personalized Medicine , published by Springer in 2009. It was translated into Japanese in 2012 and the current version is the second edition of this book. Professor Jain’s 452 publications include 25 books (5 as editor + 20 as author) and 50 special reports, which have covered important areas in biotechnology, gene therapy, and biopharmaceuticals. His important recent books include Handbook of Nanomedicine (Springer 2008; Chinese edition, Peking University Press 2011; 2nd ed Springer 2012), Handbook of Biomarkers (Springer 2010), Handbook of Neuroprotection (Springer 2010), Drug-induced Neurological Disorders , 3rd ed (Hogrefe 2011), Applications of Biotechnology in Cardiovascular Disorders (Springer 2011), Applications of Biotechnology in Neurology (Springer 2013), and Applications of Biotechnology in Oncology (Springer 2014). He has edited Applied Neurogenomics (January 2015). xi Contents 1 Basic Aspects ............................................................................................ 1 Defi nition of Personalized Medicine ........................................................ 1 History of Medical Concepts Relevant to Personalized Medicine ........... 3 Molecular Biological Basis of Personalized Medicine ............................. 6 The Human Genome ............................................................................. 6 Chromosomes ....................................................................................... 7 Genes ..................................................................................................... 8 Genetic Variations in the Human Genome ............................................ 10 Interconnected Genetic and Genomic Patterns in Human Diseases ..... 17 Basics Technologies for Developing Personalized Medicine ................... 18 Defi nitions of Technologies Relevant to Personalized Medicine ......... 18 Problems with the ICH Defi nitions of Pharmacogenomics and Pharmacogenetics ........................................................................... 19 ‘Omics’ and Personalized Medicine ......................................................... 19 Relationship of Various Technologies to Personalized Medicine ......... 20 Conventional Medicine Versus Personalized Medicine ............................ 20 Personalized Medicine and Evidence-Based Medicine ............................ 21 Role of Genetics in Future Approaches to Healthcare .............................. 21 Genetic Medicine .................................................................................. 21 Human Disease and Genes .................................................................... 22 Genetic and Environmental Interactions in Etiology of Human Diseases ............................................................................... 22 Role of Genetics in Development of Personalized Medicines .............. 23 Role of Systems Biology in Personalized Medicine ................................. 26 Systems Pharmacology ......................................................................... 27 Systems Medicine ................................................................................. 28 Synthetic Biology and Development of Personalized Medicines ............. 29 Integration of Technologies for Personalized Medicine ........................... 30 Reclassifi cation of Diseases ...................................................................... 31 Translational Science and Personalized Medicine .................................... 32 References ................................................................................................. 32 xiii xiv Contents 2 Molecular Diagnostics in Personalized
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