The Biology Of Cancer Weinberg Pdf Download
In this blog [Download] The Biology of Cancer Weinberg PDF Book. This includes information spreads through the expression of key experiments which give readers a sense of finding and provides insights into the conceptual foundation underlying modern cancer biology.
The Biology Of Cancer Weinberg Pdf Download
The chapters are meant to be read in the order that they appear, in that each builds on the ideas that have been presented in the chapters before it. The first chapter is a condensed refresher course for undergraduate biology majors and pre-doctoral students; it lays out many of the background concepts that are assumed in the subsequent chapters. The driving force of these two editions has been a belief that modern cancer research represents a conceptually coherent field of science that can be presented as a clear, logical progression.
2. the biology ofCANCER SECOND EDITIONRobert A. Weinberg 3. Thispage intentionally left blank to match pagination of print book 4.the biology ofCANCER SECOND EDITIONRobert A. Weinberg 5. GarlandScience Vice President: Denise Schanck Assistant Editor: AllieBochicchio Production Editor and Layout: EJ Publishing ServicesText Editor: Elizabeth Zayatz Copy Editor: Richard K. MickeyProofreader: Sally Huish Illustrator: Nigel Orme Designer: MatthewMcClements, Blink Studio, Ltd. Permissions Coordinator: BeckyHainz-Baxter Indexer: Bill Johncocks Director of DigitalPublishing: Michael Morales Editorial Assistant: Lamia Harik 2014by Garland Science, Taylor & Francis Group, LLCThis bookcontains information obtained from authentic and highly regardedsources. Every effort has been made to trace copyright holders andto obtain their permission for the use of copyright material.Reprinted material is quoted with permission, and sources areindicated. A wide variety of references are listed. Reasonableefforts have been made to publish reliable data and information,but the author and the publisher cannot assume responsibility forthe validity of all materials or for the consequences of their use.All rights reserved. No part of this book covered by the copyrighthereon may be reproduced or used in any format in any form or byany means graphic, electronic, or mechanical, includingphotocopying, recording, taping, or information storage andretrieval systemswithout permission of the publisher.ISBNs:978-0-8153-4219-9 (hardcover); 978-0-8153-4220-5(softcover).Library of Congress Cataloging-in-Publication DataWeinberg, Robert A. (Robert Allan), 1942The biology of cancer. --Second edition. pages cm Includes bibliographical references. ISBN978-0-8153-4219-9 (hardback) -- ISBN 978-0-8153-4220-5 (pbk.) 1.Cancer--Molecular aspects. 2. Cancer--Genetic aspects. 3. Cancercells. I. Title. RC268.4.W45 2014 616.994--dc23 2013012335Publishedby Garland Science, Taylor & Francis Group, LLC, an informabusiness, 711 Third Avenue, New York, NY 10017, USA, and 3 ParkSquare, Milton Park, Abingdon, OX14 4RN, UK.Printed in the UnitedStates of America 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1Visit ourwebsite at the Author Robert A.Weinberg is a founding member of the Whitehead Institute forBiomedical Research. He is the Daniel K. Ludwig Professor forCancer Research and the American Cancer Society Research Professorat the Massachusetts Institute of Technology (MIT). Dr. Weinberg isan internationally recognized authority on the genetic basis ofhuman cancer and was awarded the U.S. National Medal of Science in1997. Front Cover A micrograph section of a human in situ ductalcarcinoma with -smooth muscle actin stained in pink, cytokeratins 5and 6 in redorange, and cytokeratins 8 and 18 in green. (Courtesyof Werner Bcker and Igor B. Buchwalow of the Institute forHematopathology, Hamburg, Germany.) 6. vDedicationIdedicate thissecond edition, as the first one, to my dear wife, Amy ShulmanWeinberg, who endured long hours of inattention, hearing from merepeatedly the claim that the writing of this edition was almostcomplete, when in fact years of work lay ahead. She deserved muchbetter! With much love. 7. This page intentionally left blank tomatch pagination of print book 8. viiPrefaceCompared with otherareas of biological research, the science of molecular oncology isa recent arrival; its beginning can be traced with some precisionto a milestone discovery in 1975. In that year, the laboratory ofHarold Varmus and J. Michael Bishop in San Francisco, Californiademonstrated that normal cell genomes carry a genethey called it aproto-oncogenethat has the potential, following alteration, toincite cancer. Before that time, we knew essentially nothing aboutthe molecular mechanisms underlying cancer formation; since thattime an abundance of information has accumulated that now revealsin outline and fine detail how normal cells become transformed intotumor cells, and how these neoplastic cells collaborate to formlife-threatening tumors. The scientific literature on cancerpathogenesis has grown explosively and today encompasses millionsof research publications. So much information would seem to be apure blessing. After all, knowing more is always better thanknowing less. In truth, it represents an embarrassment of riches.By now, we seem to know too much, making it difficult toconceptualize cancer research as a single coherent body of sciencerather than a patchwork quilt of discoveries that bear only a vaguerelationship with one another. This book is written in a far morepositive frame of mind, which holds that this patchwork quilt isindeed a manifestation of a body of science that has some simple,underlying principles that unify these diverse discoveries. Cancerresearch is indeed a field with conceptual integrity, much likeother areas of biomedical research and even sciences like physicsand chemistry, and the bewildering diversity of the cancer researchliterature can indeed be understood through these underlyingprinciples. Prior to the pioneering findings of 1975, we knewalmost nothing about the molecular and cellular mechanisms thatcreate tumors. There were some intriguing clues lying around: Weknew that carcinogenic agents often, but not always, operate asmutagens; this suggested that mutant genes are involved in somefashion in programming the abnormal proliferation of cancer cells.We knew that the development of cancer is often a long, protractedprocess. And we knew that individual cancer cells extracted fromtumors behave very differently than their counterparts in normaltissues. Now, almost four decades later, we understand how mutantgenes govern the diverse traits of cancer cells and how the traitsof these individual cells determine the behavior of tumors. Many ofthese advances can be traced to the stunning improvements inexperimental tools. The techniques of genetic analysis, which werequite primitive at the beginning of this period, have advanced tothe stage where we can sequence entire tumor cell genomes inseveral days. (This is in sharp contrast to the state of affairs in1975, when the sequencing of oligonucleotides represented aformidable task!) Given the critical role of genotype indetermining phenotype, we now understand, as least in outline, whycancer cells behave the way that they do. On the one hand, themolecular differences among individual cancers suggest hundreds ofdistinct types of human cancer. On the other, molecular andbiochemical analyses reveal that this bewildering diversity reallymanifests a small number of underlying common biochemical traitsand molecular processes. 9. viii Preface Amusingly, much of thisunification was preordained by decisions made 600 million yearsago. Once the laws and mechanisms of organismic development wereestablished, they governed all that followed, including thebehavior of both normal and neoplastic cells. Modern cancerresearchers continue to benefit from this rigid adherence to thefundamental, evolutionarily conserved rules of life. As is evidentrepeatedly throughout this book, much of what we understand aboutcancer cells, and thus about the disease of cancer, has beenlearned by studying the cells of worms and fruit flies and frogs.These laws and principles are invoked repeatedly to explain thecomplex behaviors of human tumors. By providing context andperspective, they can be used to help us understand all types ofhuman cancer. While these basic principles are now in clear view,critical details continue to elude us. This explains why moderncancer research is still in active ferment, and why new,fascinating discoveries are being reported every month. While theycreate new perspectives, they do not threaten the solidity of theenduring truths, which this book attempts to lay out. Theseprinciples were already apparent seven years ago when the firstedition of this book appeared and, reassuringly, their credibilityhas not been undermined by all that has followed. In part, thisbook has been written as a recruiting pamphlet, as new generationsof researchers are needed to move cancer research forward. They areso important because the lessons about cancers origins, laid outextensively in this book, have not yet been successfully applied tomake major inroads into the prevention and cure of this disease.This represents the major frustration of contemporary cancerresearch: the lessons of disease causation have rarely beenfollowed, as day follows night, by the development of definitivecures. And yes, there are still major questions that remain murkyand poorly resolved. We still do not understand how cancer cellscreate the metastases that are responsible for 90% ofcancer-associated mortality. We understand rather little of therole of the immune system in preventing cancer development. Andwhile we know much about the individual signaling moleculesoperating inside individual human cells, we lack a clearunderstanding of how the complex signaling circuitry formed bythese molecules makes the life-and-death decisions that determinethe fate of individual cells within our body. Those decisionsultimately determine whether or not one of our cells begins thejourney down the long road leading to cancerous proliferation and,finally, to a life-threatening tumor. Contemporary cancer researchhas enriched numerous other areas of modern biomedical research.Consequently, much of what you will learn from this book will beuseful in understanding many aspects of immunology, neurobiology,developmental biology, and a dozen other biomedical researchfields. Enjoy the ride! Robert A. Weinberg Cambridge, MassachusettsMarch 2013 10. ixA Note to the ReaderThe second edition of thisbook is organized, like the first, into 16 chapters of quitedifferent lengths. The conceptual structure that was established inthe first edition still seemed to be highly appropriate for thesecond, and so it was retained. What has changed are the contentsof these chapters: some have changed substantially since theirfirst appearance seven years ago, while otherslargely earlychaptershave changed little. The unchanging nature of the latter isactually reassuring, since these chapters deal with earlyconceptual foundations of current molecular oncology; it would bemost unsettling if these foundational chapters had undergoneradical revision, which would indicate that the earlier edition wasa castle built on sand, with little that could be embraced aswell-established, unchanging certainties. The chapters are meant tobe read in the order that they appear, in that each builds on theideas that have been presented in the chapters before it. The firstchapter is a condensed refresher course for undergraduate biologymajors and pre-doctoral students; it lays out many of thebackground concepts that are assumed in the subsequent chapters.The driving force of these two editions has been a belief thatmodern cancer research represents a conceptually coherent field ofscience that can be presented as a clear, logical progression.Embedded in these discussions is an anticipation that much of thisinformation will one day prove useful in devising novel diagnosticand therapeutic strategies that can be deployed in oncologyclinics. Some experiments are described in detail to indicate thelogic supporting many of these concepts. You will find numerousschematic drawings, often coupled with micrographs, that will helpyou to appreciate how experimental results have been assembled,piece-by-piece, generating the syntheses that underlie molecularoncology. Scattered about the text are Sidebars, which consist ofcommentaries that represent detours from the main thrust of thediscussion. Often these Sidebars contain anecdotes or elaborate onideas presented in the main text. Read them if you are interested,or skip over them if you find them too distracting. They arepresented to provide additional interesta bit of extra seasoning inthe rich stew of ideas that constitutes contemporary research inthis area. The same can be said about the Supplementary Sidebars,which have been relegated to the DVD-ROM that accompanies thisbook. These also elaborate upon topics that are laid out in themain text and are cross-referenced throughout the book. Spaceconstraints dictated that the Supplementary Sidebars could not beincluded in the hardcopy version of the textbook. Throughout themain text you will find extensive cross-references whenever topicsunder discussion have been introduced or described elsewhere. Manyof these have been inserted in the event that you read the chaptersin an order different from their presentation here. Thesecross-references should not provoke you to continually leaf throughother chapters in order to track down cited sections or figures. Ifyou feel that you will benefit from earlier introductions to atopic, use these cross-references; otherwise, ignore them. Eachchapter ends with a forward-looking summary entitled Synopsis andProspects. This section synthesizes the main concepts of thechapter and often addresses 11. xA note to the reader ideas thatremain matters of contention. It also considers where researchmight go in the future. This overview is extended by a list of keyconcepts and a set of questions. Some of the questions aredeliberately challenging and we hope they will provoke you to thinkmore deeply about many of the issues and concepts developed.Finally, most chapters have an extensive list of articles fromresearch journals. These will be useful if you wish to explore aparticular topic in detail. Almost all of the cited references arereview articles, and many contain detailed discussions of varioussubfields of research as well as recent findings. In addition,there are occasional references to older publications that willclarify how certain lines of research developed. Perhaps the mostimportant goal of this book is to enable you to move beyond thetextbook and jump directly into the primary research literature.This explains why some of the text is directed toward teaching theelaborate, specialized vocabulary of the cancer researchliterature, and many of its terms are defined in the glossary.Boldface type has been used throughout to highlight key terms thatyou should understand. Cancer research, like most areas ofcontemporary biomedical research, is plagued by numerousabbreviations and acronyms that pepper the text of many publishedreports. The book provides a key to deciphering this alphabet soupby defining these acronyms. You will find a list of suchabbreviations in the back. Also contained in the book is a newlycompiled List of Key Techniques. This list will assist you inlocating techniques and experimental strategies used incontemporary cancer research. The DVD-ROM that accompanies the bookalso contains a PowerPoint presentation for each chapter, as wellas a companion folder that contains individual JPEG files of thebook images including figures, tables, and micrographs. Inaddition, you will find on this disc a variety of media forstudents and instructors: movies and audio recordings. There is aselection of movies that will aid in understanding some of theprocesses discussed; these movies are referenced on the first pageof the corresponding chapter in a blue box. The movies areavailable in QuickTime and WMV formats, and can be used on acomputer or transferred to a mobile device. The author has alsorecorded mini-lectures on the following topics for students andinstructors: Mutations and the Origin of Cancer, Growth Factors,p53 and Apoptosis, Metastasis, Immunology and Cancer, and CancerTherapies. These are available in MP3 format and, like the movies,are easy to transfer to other devices. These media items, as wellas future media updates, are available to students and instructorsat: On the website, qualifiedinstructors will be able to access a newly created Question Bank.The questions are written to test various levels of understandingwithin each chapter. The instructors website also offers access toinstructional resources from all of the Garland Science textbooks.For access to instructors resources please contact your GarlandScience sales representative or e-mail [email protected] Theposter entitled The Pathways of Human Cancer summarizes many of theintracellular signaling pathways implicated in tumor development.This poster has been produced and updated for the Second Edition byCell Signaling Technology. Because this book describes an area ofresearch in which new and exciting findings are being announced allthe time, some of the details and interpretations presented heremay become outdated (or, equally likely, proven to be wrong) oncethis book is in print. Still, the primary concepts presented herewill remain, as they rest on solid foundations of experimentalresults. The author and the publisher would greatly appreciate yourfeedback. Every effort has been made to minimize errors.Nonetheless, you may find them here and there, and it would be ofgreat benefit if you took the trouble to communicate them. Evenmore importantly, much of the science described herein will requirereinterpretation in coming years as new discoveries are made.Please email us at [email protected] with your suggestions, whichwill be considered for incorporation into future editions.PowerPoint is a registered trademark of the Microsoft Corporationin the United States and/or other countries. 12.xiAcknowledgmentsThe science described in this book is the opus ofa large, highly interactive research community stretching acrossthe globe. Its members have moved forward our understanding ofcancer immeasurably over the past generation. The colleagues listedbelow have helped the author in countless ways, large and small, byproviding sound advice, referring me to critical scientificliterature, analyzing complex and occasionally contentiousscientific issues, and reviewing individual chapters and providingmuch-appreciated critiques. Their scientific expertise and theirinsights into pedagogical clarity have proven to be invaluable.Their help extends and complements the help of an equally largeroster of colleagueswho helped with the preparation of the firstedition. These individuals are representatives of a community,whose members are, virtually without exception, ready and pleasedto provide a helping hand to those who request it. I am mostgrateful to them. Not listed below are the many colleagues whogenerously provided high quality versions of their publishedimages; they are acknowledged through the literature citations inthe figure legends. I would like to thank the following for theirsuggestions in preparing this edition, as well as those who helpedwith the first edition. (Those who helped on this second editionare listed immediately, while those who helped with the firstedition follow.)Second edition Eric Abbate, Janis Abkowitz, JulianAdams, Peter Adams, Gemma Alderton, Lourdes Aleman, Kari Alitalo,C. David Allis, Claudia Andl, Annika Antonsson, Paula Apsell,Steven Artandi, Carlos Arteaga, Avi Ashkenazi, Duncan Baird, AmyBaldwin, Frances Balkwill, Allan Balmain, David Bartel, JosepBaselga, Stephen Baylin, Philip Beachy, Robert Beckman, JrgenBe