New Trends in Cancer for the 21st Century [electronic resource] : Proceedings of the International Symposium on Cancer: New Trends in Cancer for the 21st Century, held November 10-13, 2002, in Valencia, Spain PDF
Preview New Trends in Cancer for the 21st Century [electronic resource] : Proceedings of the International Symposium on Cancer: New Trends in Cancer for the 21st Century, held November 10-13, 2002, in Valencia, Spain
NEW TRENDS IN CANCER FOR THE 21st CENTURY ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY Editorial Board: NATHAN BACK, State University of New York at Buffalo IRUN R. COHEN, The Weizmann Institute of Science DAVID KRITCHEVSKY, Wistar Institute ABEL LAJTHA, N. S. Kline Institute for Psychiatric Research RODOLFO PAOLETTI, University of Milan Recent Volumes in this Series Volume 524 DIPEPTIDYL AMINOPEPTIDASES IN HEALTH AND DISEASE Edited by Martin Hildebrandt, Burghard F. Klapp, Torsten Hoffmann, and Hans-Ulrich Demuth Volume 525 ADVANCES IN PROSTAGLANDIN, LEUKOTRIENE, AND OTHER BIO ACTIVE LIPID RESEARCH: Basic Science and Clinical Applications Edited by Zeliha Yazici, Giancarlo Folco, Jeffrey M. Drazen, Santosh Nigam, and Takao Shimizu Volume 526 TAURINE 5: Beginning the 21st Century Edited by John B. Lombardini, Stephen W. Schaffer, and Junichi Azuma Volume 527 DEVELOPMENTS IN TRYPTOPHAN AND SEROTONIN METABOLISM Edited by Graziella Allegri, Carlo V. L. Costa, Eugenio Ragazzi, Hans Steinhart, and Luigi Varesio Volume 528 ADAMANTIADES-BEHCET'S DISEASE Edited by Christos C. Zouboulis Volume 529 THE GENUS YERSINIA: Entering the Functional Genomic Era Edited by Mikael Skurnik, Jose Antonio Bengoechea, and Kaisa Granfors Volume 530 OXYGEN TRANSPORT TO TISSUE XXIV Edited by Jeffrey F. Dunn and Harold M. Swartz Volume 531 TROPICAL DISEASES: From Molecule to Bedside Edited by Sangkot Marzuki, Jan Verhoef, and Harm Snippe Volume 532 NEW TRENDS IN CANCER FOR THE 21st CENTURY Edited by Antonio Llombart-Bosch and Vicente Felipo A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher. NEW TRENDS IN CANCER FOR THE 21st CENTURY Edited by Antonio Llombart-Bosch University of Valencia Valencia, Spain and Vicente Felipo Valencian Foundation for Biomedical Research Valencia, Spain Springer Science+Business Media, LLC Library of Congress Cataloging-in-Publication Data International Symposium on Cancer "New Trends in Cancer for the 21st Century" (2002: Valencia, Spain) New trends in cancer for the 21st century/edited by Antonio Llombart-Bosch and Vicente Felipo. p. ; cm. — (Advances in experimental medicine and biology; v. 532) Includes bibliographical references and index. ISBN 978-1-4613-4914-3 ISBN 978-1-4615-0081-0 (eBook) DOI 10.1007/978-1-4615-0081-0 1. Cancer—Treatment—Congresses. 2. Cancer—Molecular aspects—Congresses. I. Llombart Bosch, Antonio. II. Felipo, Vicente. III. Title. IV. Series. [DNLM: 1. Neoplasms—immunology—Congresses. 2. Neoplasms—therapy—Congresses. 3. Angiogenesis Factor—therapeutic use—Congresses. 4. Antineoplastic Agents—therapeutic use—Congresses. QZ 266 1609n 2003] RC270.8.I5286 2003 616.99'406—dc21 2003047451 Proceedings of the International Symposium on Cancer: New Trends in Cancer for the 21st Century, held November 10-13, 2002, in Valencia, Spain ISBN 978-1-4613-4914-3 ©2003 Springer Science+Business Media New York Originally published by Kluwer Academic/Plenum Publishers, New York in 2003 Softcover reprint of the hardcover 1st edition 2003 http://www.wkap.nl/ 10 9 8 7 6 5 4 3 21 A C.I.P. record for this book is available from the Library of Congress All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher, with the exception of any material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Permissions for books published in Europe: [email protected] Permissions for books published in the United States of America: [email protected] In Memoriam ofMs. Ana Vines Rubert PREFACE ThisvolumecontainsthemajorityoftheconferencespresentedattheInternational Symposium onCancer"NewTrendsinCancerforthe21stCentury",held inValencia, Spain,November 10-13, 2002. This Simposium was one of the activities of the Clitedra Santiago Grisolia and of the FundacionMuseudelesCiencies"PincipeFelipe"ofValencia. It is estimated thatevery yearnearly 3million Europeans develop cancer, leading to 750.000 deaths per year. This represents a tremendous burden that cannot be ignored by politicians and citizens, taking into account that these deaths occur not only in an ageing population but also in children and in adults in the most active period oftheir lives. The probability ofcure for cancer patients, considering all types ofcancer, within the different states ofthe European Union (EU), ranges from between one fourth and one half, and the survival rates in different European populations varies widely being low in western Europe. Everybody is conscious that cancer in Europeiswithoutdoubtamajorhealthproblem.Thereforegreatereffortisneededtoachievebetter resultsindecreasingboththeincidenceandthemortality. In this sense, the European Parliament under the auspices of the European Commission Research Directorate-General has expressed the need for a more active policyin orderto develop newstrategiesinprevention,cancercareandresearch. Thefollowingneedshavebeenidentified: a) developingevidence-basedguidelinesforearlydetection,diagnosis,treatmentandafter-careforthe most common types of cancer; b) cancer research should be oriented towards a more interdisciplinaryapproachand shouldreceive more financial support; c) more research on courses oftreatment,introducingindependentclinicalassaysonahighernumberofpatients;d)comparative research on the cost-effectiveness ofvarious detection and treatment methods in order to increase efficiency and reduce costs in the health care system; e) development ofEuropean modules for continuedtraining inresearch and ofclinical specialists in the various fields; and f) to ensurethat the existingnetworkscancontinuetheirsuccessfulactivityin the future and thatnew oneswill be created. ThemainobjectiveoftheSymposium "NewTrends inCancerforthe21stCentury"wastojoin outstandingscientistsfromovertheworldwhodeveloptheiractivitiesindifferentareasofthe fight a~ainstcancer,givingthemtheopportunitytoimprovetheirknowledgeinotherareasandexchange ideasandinformation. Thecausesofcancerandthemanyfactorswhichinfluenceitsemergenceareverycomplexand heterogeneous.Themalignanttransformedcellcontainssignalsthatstimulateorinhibitthedisease and arise from the stepwise accumulation of genetic changes that confer the mutated cell the propertiesofunlimitedgrowthandresistancetohomeostaticregulatorymechanisms. Oneofthemaintargetsincanceristhecellcyclemachinerywhichiscontrolledbyanumberof extrinsic signals and tumour suppressor proteins that decide whether the cell should remain quiescent or enterinto active growthand division. This decision is mainly taken at the restriction point at the middle of the G1 phase, but there are certain checkpoints that ensure the correct transitionofeachphasethroughthecellcycle.Severalanimalmodelshavebeendevelopedwiththe aim of understanding the role played by the different elements integrating these cell cycle vii viii Preface checkpoints. These animal models may be a valuable tool to design and validate new therapeutic strategiesagainsttumordevelopment. From the pathological point of view, the diagnosis and clinical classification oftumours is based mainly upon the recognition of the microscopical tumoral pattern with the support of immunophenotypingandsomeotheremergingmoleculartechniquesthathelptodistinguishseveral tumor subtypes and grades and correlate them with the clinical stage and response to treatment. However, the molecular heterogeneity of cancer cells and of their supporting stroma and vascularization, produces numerous biological variations, within morphologically similar malignancies,thatcurrentlyescapethecurrentpossibilitiesofdiagnosisandprognosisandtherefore toarationaltherapeuticapproach.Thedevelopmentofanovelandsophisticatedtechnologyforthe study of tumour profiling, both at the genetic level (genetics and epigenetics) and at protein expression profiles (proteomics), is opening doors to what is considered the new molecular pathology. This represents an exceptional opportunity for histopathology sincewith the expansion ofalarge numberofassayable markers, it isnow possible to gather abettermolecularportrait of tumors. Most tumors acquire the capacity of invasion and metastasis and escape the barriers ofthe host's immune system. One of the main focuses of attention in this sense is the study of the phenomenon of angiogenesis: structural bases and main molecular players, as well as the therapeuticpossibilitiesthatexisttoabrogatethisprocessintumors. Ontheotherhand, stimulation ofthehostimmunesystemby meansofnewlydevelopedanti-tumoral vaccines has openedone of themostexcitingfieldsinthefightagainstcancer. Thesearchfor anddevelopmentofnewtherapeuticdrugsdirectedagainstspecifictargetssuch as inhibitors of tyrosin kinase receptors or monoclonal antibodies which down-regulate the hyperactive function of some oncogenes, has considerably improved the outcome for several patients(PhaseIIandIIIstudies)whichonthecontrarywouldhaveapproachedtotheoutcome. Specialmentioninthefightagainstcancerhastobemadeoforganizationssuchasthe EORTC (European Organization for Research and Treatment of Cancer), the OECI (Organization of European Cancer Institutes) and the comprehensive cancer centers that promote and co-ordinate high-qualitylaboratoryresearchandclinicaltrialsand also providecentral facilities with scientific expertiseandadministrativesupportforthisnetworkofscientistsandclinicalinvestigators. Thisbookprovides,therefore,an updateonthe knowledge oncertaincrucial aspectsregarding the latest aspects on research in the field of cancer, such as basic diagnostic and therapeutic research. Wewouldliketoexpressourgratitudetoall theparticipantsfortheirwrittencontributionsand fortheirenlightenedandfruitfuldiscussion. We also acknowledge withdeep gratitudethe Gomez Mata family who take the initiative and provided financial support to organize this Symposium to honour the memory ofMs Ana Vines Rubertwho diedofcancer. This represents an exceptional exampleofthe society's feelings about thisdisease. We also thank the Department of Pathology of the University of Valencia, the Fundacion Instituto Valenciano de Oncologia, the Oficina de Ciencia y Tecnologia de la Generalitat Valenciana,theCatedraSantiagoGrisoliaandtheMuseoPrincipeFelipeoftheCiudaddelasArtes y las Ciencias ofValencia, which provided the personnel and the facilities to organize both the Symposiumandthesessions. AntonioLlombart-Bosch VicenteFelipo CONTENTS DrivingtheCellCycletoCancer 1 MarcosMalumbres,SarahL. Hunt,RocioSotillo,JavierMartin,JunOdajima, AlbertoMartin,PierreDubus,SagrarioOrtega,andMarianoBarbacid Proliferation: TheCellCycle 13 ManuelSerrano MolecularAnalysisofGeneExpressioninTumorPathology..'" ,.., 19 HeinzHofler,KatjaSpecht, andKarl-FriedrichBecker EwingTumorBiology: PerspectivesforInnovativeTreatmentApproaches 27 HeinrichKovar CancerEpigenetics: DNAMethylationandChromatinAlterationsinHumanCancer .... 39 ManelEsteller MolecularAnalysisofCancerUsingDNAandProteinMicroarrays 51 JuanMadoz-GurpideandSamM. Hanash ProteomicApproachestotheDiagnosis,Treatment,andMonitoringofCancer 59 JuliaD. Wulfkuhle, CloudP.Paweletz,PatriciaS. Steeg,EmanuelF.PetricoinIII, and LanceLiotta StructuralBasisofTumoralAngiogenesis '" , 69 AntonioLlombart-Bosch,JoseA. Lopez-Guerrero,CarmenCardaBatalla,Amparo RuizSaun,andAmandoPeydro-Olaya MatrixMetalloproteinasesandTumorProgression 91 JoseM.P. Freije, MilagrosBalbin, AlbertoM. Pendas, LuisM. Sanchez, XoseS.Puente,and CarlosLopez-Otin AngiogenesisInhibitorsand TheirTherapeuticPotentials 109 Yihai Cao ix x Contents MutatedTyrosineKinases asTherapeuticTargetsinMyeloidLeukemias 121 MartinSattler,BlancaScheijen,EllenWeisberg, andJamesD. Griffin TargetingPDGFReceptorsinCancer- RationalesandProofofConceptClinical Trials 141 DanielGeorge Immune-PromotedTumorCellInvasionandMetastasis. Newconsiderations incancertherapy 153 EmilioBarberaGuillem andJames W. Sampsel ImprovementsofSurvivalinNinePhaseIIClinicalStudiesWithDifferentTypesof CancerUponAnti-TumorVaccinationwithanAutologousTumorCellVaccine ModifiedbyVirus InfectiontoIntroduceDangerSignals 175 VolkerSchirrmacher CausationandPreventionofSolelyEstrogen-InducedOncogenesis: Similarities toHumanDuctalBreastCancer 195 JonathanJ. Liand SaraAntoniaLi Cyclooxygenase-2InhibitorsinCancerPreventionandTreatment 209 JaimeL.Masferrer ExosomesforImmunotherapyofCancer 215 NathalieChaput,NECSchartz,FabriceAndre, and LaurenceZitvogel BreastCancerGeneExpressionAnalysis- TheCaseforDynamicProfiling 223 MatthewJ. Ellis DevelopmentoftheEpidermalGrowthFactorReceptorInhibitor TARCEVATM (OSI-774) 235 ViktorGIiinwaldandManuelHidalgo Gefitinib(IRESSA,ZD 1839)forNon-SmallCellLungCancer(NSCLC): RecentsResultsandFurtherStrategies 247 ChristianManegold MechanismofActionofAnti-HER2Monoclonal Antibodies: ScientificUpdateon Trastuzumaband2C4 253 JoanAlbanell,JordiCodony, AnaRovira, BegofiaMellado,andPereGascon EORTCResearchandDevelopment:AchievementsandFuturePerspectives 269 DenisLacombe,RalphCrott,andFranyoiseMeunier Contributors 277 Index 283
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