Tumor Angiogenesis. A Key Target for Cancer Therapy PDF
Preview Tumor Angiogenesis. A Key Target for Cancer Therapy
Dieter Marmé Editor Tumor Angiogenesis A Key Target for Cancer Therapy Tumor Angiogenesis Dieter Marmé Editor Tumor Angiogenesis A Key Target for Cancer Therapy With63Figuresand42Tables Editor DieterMarmé TumorBiologyCenter Freiburg,Baden-Württemberg,Germany ISBN978-3-319-33671-8 ISBN978-3-319-33673-2(eBook) ISBN978-3-319-33672-5(printandelectronicbundle) https://doi.org/10.1007/978-3-319-33673-2 ©SpringerNatureSwitzerlandAG2019 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeor part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations,recitation,broadcasting,reproductiononmicrofilmsorinanyotherphysicalway, andtransmissionorinformationstorageandretrieval,electronicadaptation,computersoftware,or bysimilarordissimilarmethodologynowknownorhereafterdeveloped. Theuseofgeneraldescriptivenames,registerednames,trademarks,servicemarks,etc.inthis publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexempt fromtherelevantprotectivelawsandregulationsandthereforefreeforgeneraluse. Thepublisher,theauthors,andtheeditorsaresafetoassumethattheadviceandinformationinthis bookarebelievedtobetrueandaccurateatthedateofpublication.Neitherthepublishernorthe authorsortheeditorsgiveawarranty,expressorimplied,withrespecttothematerialcontained hereinorforanyerrorsoromissionsthatmayhavebeenmade.Thepublisherremainsneutralwith regardtojurisdictionalclaimsinpublishedmapsandinstitutionalaffiliations. ThisSpringerimprintispublishedbytheregisteredcompanySpringerNatureSwitzerlandAG. Theregisteredcompanyaddressis:Gewerbestrasse11,6330Cham,Switzerland ThisworkisdedicatedtomygrandchildrenAnn-Sophie,Aurélie, and Mathis Foreword Itisnowalmost50yearssinceJudahFolkmanpublishedin1971thelegendary hypothesispaperintheNewEnglandJournalofMedicinethatstartedthefield ofmodernangiogenesisresearch.Folkmanpredictedtheexistenceofatumor angiogenesis factor (TAF) that would induce the growth of blood vessels in tumorsandwhoseblockadewouldleadtotheregressionofgrowingtumorsto maintainthemindormantstateatmicroscopicsize.Manyangiogenicgrowth factors have been identified since then, but if any one factor comes close to being TAF, it is the vascular endothelial growth factor (VEGF) family of molecules, most notably VEGF-A. VEGF-A stands high up in the hierarchy ofevents thatinduce thesproutingofcapillaries from existing microvessels. Discovered by Napoleone Ferrara in 1989, it took 15 years from target discoverytoclinicalapprovalofthefirstVEGFblockingdrug,theneutralizing antibodyBevacizumab.BevacizumabandseveralotherVEGFblockingdrugs aswellasapanelofVEGFreceptorneutralizingorblockingdrugsarenowin clinicaluseinthefieldsofoncologyandophthalmology.Withseveralblock- buster drugs generating revenues of more than 1 billion USD per year, the total market of anti-angiogenic drugs is well exceeding 10 billion USD. Anti-angiogenictumortherapyhastherebybecomethefirstclinicallyeffective anti-stromatherapypartofstandardtumortherapy.Yet,itclearlydidnotlive up to the high public expectations that anti-angiogenic tumor therapies were expectedtoexertaroundtheturnofthecentury.Instead,theoveralltherapeutic benefit is modest resulting in an increase of patients’ overall survival in the range of week to months (e.g., from 15.6 to 20.3 months for patient with metastatic colorectal cancers). Still, in terms of percentage, this reflects a highlysignificantincreaseinoverallsurvivalof25%. Manytextbooksontumorangiogenesishavebeenpublishedduringthelast decades probablyraising thequestion whyanothertextbookisneeded when the major questions in the field of angiogenesis research have apparently all beenanswered.Well,havethey?Probablynot,becausekeyquestionsremain unanswered.Themechanismsofactionofanti-angiogenictumortherapy(i.e., regressionvs.normalization)aretothisdaynotwellunderstood,particularly inhumantumors.Nostratifyingprocedureshavebeendevelopedthatwould becapableofpredictingtheresponsetoanti-angiogenictherapy.Theadventof immuno-oncology (IO) drugs raises a whole plethora of questions on the rationale combination of anti-angiogenic drugs and IO drugs (stromal reprogramming to improve the efficacy of IO drugs). Most importantly, has vii viii Foreword the full potential of anti-angiogenic therapy already been exploited? Combi- nationsofVEGF-targetingandangiopoietin-targeting drugs, inrecent years, didnotyieldtheanticipatedsynergisticeffects.Still,theremayberoomforthe development of novel combinatorial drugs targeting vascular sprouting and vascularmaturation. Givenalltheseenigmaticquestions,thebookTumorAngiogenesis:AKey TargetforCancerTherapy,editedbyDieterMarmé,servesasatimelyupdate on a research field that may still hold many surprises in terms of biological mechanisms andphenomenaas well astranslational windowofopportunity. More than 30 chapters cover, on the one hand, all relevant molecular and mechanistic aspects and zoom in, on the other hand, on the specific organ attributes of angiogenesis and anti-angiogenic therapy in 15 different tumor entities.Itisthiscombinationthatwillmakethebookausefulresourceforthe experienced and newcomer basic scientist in the field as well as for clinical scientists interested in specific tumor entities. The future will unravel the potentialofvasculartargetedtherapiesinoncologyandbeyond.Butinorder to get there, much needs to be learned about organ-specific functions of organotypically differentiated blood vessels in health and diseases. Tumor Angiogenesismayserveasamostwelcomealertthatindeednotallquestions have been answered and likewise that the full potential of anti-angiogenic therapyhasnotyetbeenexploited. Heidelberg HellmutG.Augustin April2019 Acknowledgments TheEditorwouldliketoacknowledgetheextraordinaryhelpfulassistanceof Springer’sBarbaraWolfandJohannaKlute. It was always a good feeling to be able to rely on their outstanding organizationalskillsandtheirhelpinallmatters. ix Contents PartI MechanismsofTumorAngiogenesis .................. 1 MechanismsofTumorAngiogenesis ........................ 3 IratxeZuazo-GazteluandOriolCasanovas TheRoleofVEGFinControllingVascularPermeability ........ 33 LakshmiVenkatramanandLenaClaesson-Welsh BenefitsandPitfallsofTumorVesselNormalization ........... 51 Jin-SungPark,IntaePark,andGouYoungKoh TheImpactofEndothelialTranscriptionFactorsinSprouting Angiogenesis ............................................ 73 MelanieHofmannandJoergHeineke EndothelialCell-CellJunctionsinTumorAngiogenesis ......... 91 QuentinRouxandJulieGavard ControllingVascularPermeability:HowDoesItWorkandWhat IstheImpactonNormalandPathologicalAngiogenesis ........ 121 IngaBekesandChristineWulff PartII MechanismsofTumorLymphangiogenesis ........... 133 AngiopoietinsandTIEReceptorsinLymphangiogenesisand TumorMetastasis ....................................... 135 YulongHe SignificanceandMolecularRegulationofLymphangiogenesis inCancer .............................................. 157 MihaelaSkobeandBronislawPytowski PartIII MechanismsofAnti-angiogenicTherapy ............ 181 MechanismsofAnti-angiogenicTherapy .................... 183 RoserPons-CursachandOriolCasanovas xi xii Contents PartIV Anti-angiogenicTargets ............................ 209 TheRoleoftheVEGFSignalingPathwayinTumor Angiogenesis ............................................ 211 NapoleoneFerrara Anti-angiogenicTargets:Angiopoietinand AngiopoietinReceptors ................................... 227 ElinaA.KissandPipsaSaharinen PartV PathologyofTumorAngiogenesis ................... 251 PathologyofTumorAngiogenesis .......................... 253 PeterBronsertandMartinWerner PartVI ImagingofTumorAngiogenesis .................... 275 ImagingTumorAngiogenesis .............................. 277 GordonJaysonandJamesO’Connor PartVII BiomarkersforAnti-angiogenicTherapy ............ 291 BiomarkersforAnti-angiogenicTherapy .................... 293 WeibinHouandStefanDuensing PartVIII MechanismsofResistanceinAnti-angiogenic Therapy .................................................... 311 Anti-angiogenicCancerTherapy:DevelopmentofResistance .... 313 DomenicoRibatti PartIX MechanismsofSynergyinCombinationsof Anti-angiogenicsandOtherTargetedTherapies .............. 325 CytotoxicsandAnti-angiogenics:MetronomicTherapies ....... 327 AndreasPircher,NormannSteiner,andEberhardGunsilius Anti-angiogenicsandRadiationTherapy .................... 349 DanielH.Schanne,Anca-L.Grosu,andDanG.Duda CombinationofAnti-angiogenicsandOtherTargeted Therapies .............................................. 359 KatjaZirlikandJustusDuyster PartX Anti-angiogenicsinGastrointestinalCancers ......... 377 Anti-angiogenicTargetinginMetastaticColorectalCancer Therapy ............................................... 379 ThomasZander,ValentinGoede,andMichaelHallek
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