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<p>About the Editor xi</p> <p>Contributors xiii</p> <p>Foreword xxi</p> <p>Preface xxiii</p> <p>Acknowledgments xxxv</p> <p><b>Section I Essentials of Cancer Stem Cells and Conceptual Modeling 1</b></p> <p>1 Theoretical and Experimental Foundations of the "Cancer Stem Cell" Model 3<br /> <i>Pradeep S. Rajendran and Piero Dalerba</i></p> <p>2 The Hallmarks of Prostate Cancer Stem Cells 17<br /> <i>Norman J. Maitland and Anne T. Collins</i></p> <p>3 Self-Renewal, Induced Proliferation, and Autonomous Cell Growth Represent Distinct Modes of Cell Multiplication: Relevance to the Cancer Stem Cell Theory 39<br /> <i>Dov Zipori</i></p> <p>4 Human Embryonic Stem Cells and Cancer: Modeling Disease in a Dish 49<br /> <i>Tamra Werbowetski-Ogilvie and Robyn McClelland</i></p> <p>5 Cancer Stem Cell as a Result of a Reprogramming-Like Mechanism: Implications in Tumor Development and Treatment 61<br /> <i>J.M. Iglesias, Idoia Garcia-Ramirez, Alberto Martin-Lorenzo, L. Vellon, Lucia Ruiz-Roca, A.G. Martin, and Isidro Sanchez-Garcia</i></p> <p>6 A Cancer Stem Cell Model: An Insight into the Conversion of Induced Pluripotent Stem Cells to Cancer Stem-Like Cells 79<br /> <i>Akifumi Mizutani, Ling Chen, Tomonari Kasai, Takayuki Kudoh, Hiroshi Murakami, Li Fu, and Masaharu Seno</i></p> <p>7 Altruistic Stem Cells and Cancer Stem Cells 89<br /> <i>Bikul Das</i></p> <p>8 The Emerging Concept of EMT-Induced Cancer Stem Cells 107<br /> <i>Jeremy Bastid</i></p> <p>9 Models to Study Chronic Myeloid Leukemia Cancer Stem Cells 119<br /> <i>Sheela A. Abraham, Lisa Hopcroft, Ravi Bhatia, Steffen Koschmieder, Anthony D. Whetton, and Tessa L. Holyoake</i></p> <p>10 Cancer Stem Cells in Melanoma: Biomarkers and Mathematical Models 133<br /> <i>Stefano Zapperi and Caterina A.M. La Porta</i></p> <p><b>Section II Stem Cells in Liquid Tumors 143</b></p> <p>11 Acute Myeloid Leukemia Stem Cells—Updates and Controversies 145<br /> <i>Stephen S. Chung and Christopher Y. Park</i></p> <p>12 Leukemia-Initiating Cells in Acute Lymphoblastic Leukemia 161<br /> <i>Thorsten Raff and Monika Brüggemann</i></p> <p><b>Section III Stem Cells in Solid Tumors 171</b></p> <p>13 Lung Cancer Stem Cells and Resistance to Radiotherapy 173<br /> <i>Scott V. Bratman and Maximilian Diehn</i></p> <p>14 Prostate Cancer Cell Heterogeneity and Prostate Cancer Stem Cells 183<br /> <i>Mark A. Badeaux and Dean G. Tang</i></p> <p>15 Glioblastoma Stem Cells Drive Tumor Recurrence and Patient Relapse: What's the Evidence? 193<br /> <i>Aneet Mann, Randy van Ommeren, Branavan Manoranjan, Nicole McFarlane, Parvez Vora, Chitra Venugopal, and Sheila Singh</i></p> <p>16 Stem Cells and Pancreatic Cancer 209<br /> <i>Susana Garcia-Silva and Christopher Heeschen</i></p> <p>17 Melanoma Subpopulations with Cancer Stem Cell Phenotypes 223<br /> <i>Rajasekharan Somasundaram, Nicole Facompre, and Meenhard Herlyn</i></p> <p>18 Sarcoma Stem Cells 235<br /> <i>Filemon S. Dela Cruz and Igor Matushansky</i></p> <p><b>Section IV Cancer Stem Cells in Tumor Metastasis Perspective 247</b></p> <p>19 Cancer Stem Cells in Metastasis and Minimal Residual Disease 249<br /> <i>Joerg Huelsken and Albert Santamaria i Martinez</i></p> <p>20 Role of Cancer Stem Cells in Metastasis 259<br /> <i>Giovanna Merchand-Reyes, Rosana Pelayo, Lenin Pavón, Richard G. Pestell, and Marco Velasco-Velázquez</i></p> <p>21 Cancer Stem Cells and the Stromal Microenvironment 273<br /> <i>Li Li and David A. Margolin</i></p> <p>22 A Perspective on Breast Cancer Malignant Progression: From Cancer Stem Cell Intra Tumor Heterogeneity to Metastasis-Initiating Cells 287<br /> <i>Pasquale Sansone, Vinagolu K. Rajasekhar, and Jacqueline Bromberg</i></p> <p><b>Section V Novel and Potential Targets in Cancer Stem Cells 295</b></p> <p>23 Targeting Cancer Stem Cells—Modulating Embryonic Stem Cell Signaling, Epigenetics, and Tumor Metabolism 297<br /> <i>Naoko Takebe, Pamela Jo Harris, Yutaka Kondo, Abhilasha Nair, S. Percy Ivy, and Hideyuki Saya</i></p> <p>24 Oct4, Oct1, and Cancer Stem Cells 319<br /> <i>Jessica Maddox and Dean Tantin</i></p> <p>25 The Role of Cripto-1 in Cancer and Cancer Stem Cells 331<br /> <i>Hideaki Karasawa, Nadia P. Castro, Maria Cristina Rangel, and David S. Salomon</i></p> <p>26 Leptin Signaling in the Regulation of Stem and Cancer Stem Cells 347<br /> <i>Shanchun Guo, Keshav K. Singh, James W. Lillard, and Lily Yang</i></p> <p>27 Tumor-Initiating Stem-Like Cells: Carcinogenesis through Toll-Like Receptors, Environmental Factors, and Virus 361<br /> <i>Keigo Machida</i></p> <p>28 The Role of Epithelial Cell Polarity Pathways on Cancer Stem Cells 373<br /> <i>Inmaculada Banon-Rodriguez, Ilenia Bernascone, and Fernando Martin-Belmonte</i></p> <p>29 Cancer-Initiating Cells, Exosomes, and the Premetastatic Niche 389<br /> <i>Margot Zöller</i></p> <p>30 MicroRNA Therapeutics to Target Brain Tumor Stem Cells 403<br /> <i>Derryn Xin Hui Chan, Srikanth Nama, Gopinath Sundaram, and Prabha Sampath</i></p> <p>31 The Riboproteome Orchestrates Self-Renewal and Cell Fate in Leukemia 417<br /> <i>Elianna M. Amin and Michael G. Kharas</i></p> <p><b>Section VI Clinical Relevance of Cancer Stem Cells in Patients 435</b></p> <p>32 Targeting Different States of Breast Cancer Stem Cells 437<br /> <i>Sean P. McDermott and Max S. Wicha</i></p> <p>33 Difficulties in Targeting the Beating Heart: Therapeutic Implications of the Cancer Stem Cell Hypothesis in Melanoma 451<br /> <i>Jennifer Makalowski and Hinrich Abken</i></p> <p>34 Targeting Cancer Stem Cells for Overcoming Drug Resistance and Cancer Progression 461<br /> <i>Yiwei Li, Dejuan Kong, Aamir Ahmad, Bin Bao, and Fazlul H. Sarkar</i></p> <p>35 The Role of Cancer Stem Cells in Tumor Radioresistance 473<br /> <i>I. Kurth, C. Peitzsch, M. Baumann, and A. Dubrovska</i></p> <p>Index 493</p> <p>Color plate located between pages 222 and 223.</p>

<p>During the last decade, the conceptual themes of stem cell biology have been re-applied, with a new vigor, to the field of oncology. The idea that, similar to normal tissues, tumors can be viewed as <i>“complex societies”</i>, where different cell types are generated as the result of multi-lineage differentiation processes, and organize themselves in hierarchical structures, has now entered the realm of solid tumor biology, and altered the way we think of cancer as a disease. Most importantly, the possibility that tumor tissues, similar to normal ones, might be sustained in their long-term growth by a subset of cancer  cells endowed with stem cell properties (i.e. a mutated <i>“cancer stem cell”</i> population capable of both aberrant self-renewal as well as differentiation) has important implications for the future development of targeted therapies. In this beautiful book, Dr. Vinagolu K. Rajasekhar (<i>Memorial Sloan Kettering Cancer Center - New York</i>) thoughtfully weaved together the perspectives and contributions from several of the leading scientists in the field. This book is both an elegant review and a practical guide to the exciting, and still largely uncharted, world of <i>“cancer stem cells”</i>. I praise the editor and the authors for this wonderful endeavor, rich of provocative ideas and challenging concepts, not only for a better understanding of basic cancer biology, but also for the future development of new, more effective, anti-tumor treatments.<br /> —<b><i>Michael F. Clarke, MD., Stanford University, Stanford, CA. USA.</i></b></p> <p> “The cancer stem cell (CSC) concept posits that not all cells in tumors are equal, but that dedicated cells fuel tumor growth. A major attraction of the CSC concept rests in the explanations it provides for several poorly understood clinical phenomena. The CSCs are built to last a life-time, to be resilient to electromagnetic and chemical insults, to be able to slumber for prolonged periods of time and to colonize other parts of the body. Thus, the CSC hypothesis explains why a cancer patient should never be considered cured, even when the initial response to radiation or chemo-therapy is encouragingly robust. The concept guides the development of more effective treatments, targeting the ‘beating heart’ of the tumor: the CSC. This authoritative book, written by a range of world-leading cancer researchers, provides a comprehensive overview of the cancer stem cell, its microenvironment, and how these insights will lead to novel clinical strategies.”<br /> —<b><i>Hans Clevers, MD., PhD.,  Hubrecht Institute, Utrecht. The Netherlands.</i></b><b><i> </i></b></p> <p> “The nature and clinical relevance of cancer stem cells are timely topics covered with an appropriately broad and insightful brush in this comprehensive book devoted entirely to this subject. Chapters include emerging provocative evidence that a cancer stem cell, although still necessarily defined operationally, actually refers to a molecular state that may be unstable or altered reversibly. In this respect, the cancer stem cell field has entered a new era of complexity building on discoveries of concurrent intrinsic and extrinsic regulators of the stem cell state in normal tissues. Nevertheless, in spite of this evolution, many investigations in specific types of malignancies have proven useful and more are expected. For those wanting to stay abreast of the field from a basic as well as a clinical perspective, this book will be a welcome read and resource.”<br /> —<b><i>Connie J. Eaves, PhD., FRSC., Terry Fox Laboratory, Vancouver, Canada.</i></b></p> <p>"Cancer stem cells have moved onto center stage for those who are interested in the behavior of solid tumors. In the context of carcinomas, these cells hold the prospect of explaining many aspects of the malignant behavior of high-grade tumor cells, including their metastatic dissemination and their responsiveness to a variety of therapies. Those who are interested in developing novel therapeutic strategies for treating solid tumors can no longer afford to ignore these important subpopulations of cancer cells, which increasingly appear to be critical determinants of the success or failure of existing treatments.  This volume reports on many aspects of these cells in a variety of human tumors, justifying the notion that CSCs are likely to be important players in virtually all types of human tumors."<br /> <b><i>—Robert A. Weinberg, PhD., Whitehead Institute, Massachusetts Institute of Technology, Cambridge,  MA. USA</i></b>.</p>

<p><b>Dr. V.K. Rajasekhar</b>, M.Sc., M.Phil., Ph.D., is a Senior Research Scientist at Memorial Sloan-Kettering Cancer Center, New York.  His work with patient derived prostate cancer stem cell xenografts, a first study in renewable Biobanking of these clinically relevant cells, has garnered eclectic post-publication reviews. Dr. Rajasekhar has received competitive research awards from the Alexander von Humboldt Foundation, Germany, and the Robert A. Welch Foundation, Texas. He has conducted research at MD Anderson Cancer Center in Houston, University of California at Irvine, University of Freiburg in Germany, etc., and taught at the University of California, Irvine and the University of Medicine and Dentistry of New Jersey. Dr. Rajasekhar has served as a peer reviewer for several journals, including <i>Stem Cells, Proceedings of National Academy of Sciences USA, Journal of Molecular Biology, Journal of Cell Biology, Neoplasia,</i> etc. </p>

<i>Cancer Stem Cells</i> covers a wide range of topics in cancer stem cell biology, including the functional characteristics of cancer stem cells and how they're generated, where they are localized, the means by which cancer stem cells can be targeted, and how cancer stem cells can be reprogrammed back at least epigenetically  into non-tumor forming cells. <p>The book builds systematically from coverage of the basic research stage to an advanced research level, from clinical relevance to therapeutic potential, and will be a valuable resource for professionals in the fields of cancer research and stem cell biology.</p> <p>"This book is both an elegant review and a practical guide to the exciting, and still largely uncharted, world of <i>cancer stem cells</i>. I praise the editor and the authors for this wonderful endeavor, rich of provocative ideas and challenging concepts, not only for a better understanding of basic cancer biology, but also for the future development of new, more effective, anti-tumor treatments."<br /> —<b>Michael F. Clarke, MD., Stanford University</b></p> <p>"This authoritative book, written by a range of world-leading cancer researchers, provides a comprehensive overview of the cancer stem cell, its microenvironment, and how these insights will lead to novel clinical strategies."<br /> —<b>Hans Clevers, MD., PhD., Hubrecht Institute, Utrecht</b></p> <p>"For those wanting to stay abreast of the field from a basic as well as a clinical perspective, this book will be a welcome read and resource."<br /> —<b>Connie J. Eaves, PhD., FRSC., Terry Fox Laboratory, Vancouver</b></p> <p>"This volume reports on many aspects of these cells in a variety of human tumors, justifying the notion that CSCs are likely to be important players in virtually all types of human tumors."<br /> —<b>Robert A. Weinberg, PhD., Whitehead Institute, Massachusetts Institute of Technology</b></p>

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