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Molecular Oncology
Causes of Cancer and Targets for Treatment
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Molecular Oncology
Causes of Cancer and Targets for Treatment
Editedby
EdwardP.Gelmann
Chief,DivisionofHematology/OncologyandDeputyDirectorforClinicalResearch,HerbertIrvingComprehensiveCancerCenter
andColumbiaUniversityMedicalCenter,NewYork,NY,USA
CharlesL.Sawyers
Chair,HumanOncologyandPathogenesisProgram,MemorialSloan-KetteringCancerCenter,NewYork,NY,USA
FrankJ.RauscherIII
Professor,GeneExpressionandRegulationProgram;Professor,TumorMicroenvironmentandMetastasisProgram;
DeputyDirectorforBasicResearch,WistarInstituteCancerCenter,Philadelphia,PA,USA
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UniversityPrintingHouse,CambridgeCB28BS,UnitedKingdom
PublishedintheUnitedStatesofAmericabyCambridgeUniversity
Press,NewYork
CambridgeUniversityPressispartoftheUniversityofCambridge.
ItfurtherstheUniversity’smissionbydisseminatingknowledgeinthe
pursuitofeducation,learningandresearchatthehighest
internationallevelsofexcellence.
www.cambridge.org
Informationonthistitle:www.cambridge.org/9780521876629
(cid:2)C CambridgeUniversityPress2014
Thispublicationisincopyright.Subjecttostatutoryexception
andtotheprovisionsofrelevantcollectivelicensingagreements,
noreproductionofanypartmaytakeplacewithoutthewritten
permissionofCambridgeUniversityPress.
Firstpublished2014
PrintedintheUnitedKingdombyMPGPrintgroupLtd,Cambridge
AcatalogrecordforthispublicationisavailablefromtheBritishLibrary
LibraryofCongressCataloginginPublicationdata
Molecularoncology:causesofcancerandtargetsfortreatment/
editedbyEdwardP.Gelmann,chief,Divisionof
Hematology/OncologyanddeputydirectorforClinicalResearch,
HerbertIrvingComprehensiveCancerCenterandColumbia
UniversityMedicalCenter,NewYork,NY,USA,CharlesL.Sawyers,
chair,HumanOncologyandPathogenesisProgram,Memorial
Sloan-KetteringCancerCenter,NewYork,NY,USA,FrankJ.
RauscherIII,professor,GeneExpressionandRegulationProgram,
professor,TumorMicroenvironmentandMetastasisProgram,deputy
directorforBasicResearch,WistarInstituteCancerCenter,
Philadelphia,PA,USA.
pages cm
Includesbibliographicalreferencesandindex.
ISBN978-0-521-87662-9(hardback)
1.Cancer–Molecularaspects. 2.Tumormarkers.
3.Carcinogenesis. I.Gelmann,EdwardP.,1953– II.Sawyers,
CharlesL. III.Rauscher,F.J.(FrankJoseph),1957–
RC268.4.M675 2014
616.99(cid:3)4–dc23 2013012165
ISBN978-0-521-87662-9Hardback
CambridgeUniversityPresshasnoresponsibilityforthepersistence
oraccuracyofURLsforexternalorthird-partyinternetwebsites
referredtointhispublication,anddoesnotguaranteethatany
contentonsuchwebsitesis,orwillremain,accurateorappropriate.
................................................................
Everyefforthasbeenmadeinpreparingthisbooktoprovideaccurate
andup-to-dateinformationwhichisinaccordwithaccepted
standardsandpracticeatthetimeofpublication.Althoughcase
historiesaredrawnfromactualcases,everyefforthasbeenmadeto
disguisetheidentitiesoftheindividualsinvolved.Nevertheless,the
authors,editors,andpublisherscanmakenowarrantiesthatthe
informationcontainedhereinistotallyfreefromerror,notleast
becauseclinicalstandardsareconstantlychangingthroughresearch
andregulation.Theauthors,editors,andpublishersthereforedisclaim
allliabilityfordirectorconsequentialdamagesresultingfromtheuse
ofmaterialcontainedinthisbook.Readersarestronglyadvisedtopay
carefulattentiontoinformationprovidedbythemanufacturerofany
drugsorequipmentthattheyplantouse.
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Thisbookisdedicatedtothescientistswhomadethediscoveries,
tothemembersofindustrywhodevelopedthepharmaceuticals,
totheclinicianswhosetrialsturnedmedicinesintotherapies,
andtothepatientswhoseparticipationinresearchis
essentialandwhosediseasesweworktorelieve.
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Contents
Listofcontributors xi 11. Theinsulin–insulin-likegrowth-factorreceptor
Preface xxi familyasatherapeutictargetinoncology 110
MichaelPollak
Part1.1 Analyticaltechniques:analysisofDNA
12. TGF-(cid:2)signalinginstemcellsand
1. Cancergenomesequencing 1 tumorigenesis 119
AbizarLakdawalla,JeffreyFisher,MostafaRonaghi,and YingLiandLopaMishra
Jian-BingFan
13. Platelet-derivedgrowthfactor 131
2. Genome-wideassociationstudiesofcancer ArneO¨stmanandCarl-HenrikHeldin
predisposition 10
14. FMS-relatedtyrosinekinase3 140
ZsofiaK.Stadler,SohelaShah,andKennethOffit
SoheilMeshinchiandDerekL.Stirewalt
3. Comparativegenomichybridization 21
15. ALK:Anaplasticlymphomakinase 158
DonnaG.AlbertsonandDanielPinkel
KarenPulford
4. Chromosomeanalysis:molecularcytogenetic
16. TheFGFsignalingaxisinprostate
approaches 28
tumorigenesis 186
ThomasRied
FenWang,YongdeLuo,andWallaceL.McKeehan
5. DNAmethylation 37
17. Hepatocytegrowthfactor/Metsignaling
MarshaReyngoldandTimothyA.Chan
incancer 200
FabiolaCecchi,YoungH.Lee,andDonaldP.Bottaro
Part1.2 Analyticaltechniques:analysisofRNA
18. PI3K 214
KevinD.CourtneyandLewisC.Cantley
6. Theapplicationofhigh-throughputanalysesto
cancerdiagnosisandprognosis 46 19. Intra-cellulartyrosinekinase 227
EdwardP.Gelmann RosalynB.IrbyandTimothyJ.Yeatman
7. Cancerproteomics 52 20. WNTsignalinginneoplasia 239
S.HanashandA.Taguchi MasuraKatoh
8. Tyrosinekinomeprofiling:oncogenicmutations 21. Ras 254
andtherapeutictargetingincancer 58 AdrienneD.CoxandMollyJ.DeCristo
ParamitaGhosh,YunQiu,Ling-YuWang,and
22. BRAFmutationsinhumancancer:biologicand
Hsing-JienKung
therapeuticimplications 268
9. Insitutechniquesforproteinanalysisintumor MoriahH.NissanandDavidB.Solit
tissue 76
23. Aurorakinasesincancer:anopportunityfor
ValsamoK.AnagnostouandDavidL.Rimm
targetedtherapy 274
VikasSehdev,AltafA.Dar,andWaelEl-Rifai
Part2.1 Molecularpathwaysunderlying
24. 14-3-3proteinsincancer 289
carcinogenesis:signaltransduction AlexandraK.GardinoandMichaelB.Yaffe
10. HER 85 25. STATsignalingasamoleculartargetforcancer
therapy 301
WolfgangJ.Ko¨stlerandYosefYarden
HuaYuandRichardJove
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Contents
26. TheMYConcogenefamilyinhuman 37. Telomerase:targetforcancertreatment 438
cancer 309 JerryW.ShayandWoodringE.Wright
MichaelD.Cole
27. JunproteinsandAP-1intumorigenesis 315 Part2.5 Molecularpathwaysunderlying
ShiraAnziandEitanShaulian
carcinogenesis:cellcycle
28. Forkheadboxproteins:thetuning
forksincancerdevelopmentand 38. Cellcycle:mechanismsofcontrolanddysregulation
treatment 324 incancer 448
Chuay-YengKoo,KyleW.Muir,and ErikS.Knudsen,RyanJ.Bourgo,ElizabethL.Gosnell,
EricW.F.Lam JeffryL.Dean,andA.KathleenMcClendon
29. NF-(cid:3)Bandcancer 332 39. DNAdamage-inducedapoptosis 461
WillscottE.NauglerandMichaelKarin ShunJ.Lee,BenjaminF.O’Connor,ScottA.Stuart,and
JeanY.J.Wang
Part2.2 Molecularpathwaysunderlying
Part2.6 Molecularpathwaysunderlying
carcinogenesis:apoptosis
carcinogenesis:otherpathways
30. Apoptosis:theextrinsicpathway 349
XinchenTengandJ.MarieHardwick 40. Theubiquitin/proteasomepathwayin
neoplasia 469
31. Apoptosis:theintrinsicpathway 363
RobertC.A.M.vanWaardenburgand
JodyWhite
Mary-AnnBjornsti
41. Smallsilencingnon-codingRNAs:cancer
Part2.3 Molecularpathwaysunderlying
connectionsandsignificance 477
carcinogenesis:nuclearreceptors MilenaS.NicolosoandGeorgeA.Calin
32. Androgensandtheandrogenreceptor(AR) 374
Part3.1 Molecularpathology:carcinomas
NicoleL.Moore,MargaretM.Centenera,
LisaM.Butler,TheresaE.Hickey,and
42. Headandneckcancer 493
WayneD.Tilley
KellyQuesnelle,JenniferGrandis,KarlMunger,and
33. Emergingrolesofperoxisome MarshallR.Posner
proliferator-activatedreceptorgamma
43. Lungcancer 502
incancer 388
JillE.LarsenandJohnD.Minna
ChenguangWang,XueminZhang,and
RichardG.Pestell 44. Esophagealcancer 522
DuyKhanhPhamandThomasA.D’Amico
Part2.4 Molecularpathwaysunderlying 45. Gastriccancer 528
YoshiakiItoandKhayGuanYeoh
carcinogenesis:DNArepair
46. Small-boweltumors:molecularmechanismsand
34. TheATM-mediatedDNAdamageresponse 399 targetedtherapy 537
YosefShiloh AllanSpigelmanandJanindraWarusavitarne
35. Wernersyndrome:associationofprematureaging 47. Colonandrectalcancer 542
andcancerpredisposition 419 ErinM.PerchiniakandJoannaGroden
ByungchanAhn,TinnaStevnsner,and
48. Pancreaticcancer 551
VilhelmA.Bohr
Siong-SengLiauandDavidA.Tuveson
36. HereditarydisordersofDNArepairandDNA
49. Hepatocellularcarcinoma 563
damagetolerancethatpredisposetoneoplastic
transformation 430 AugustoVillanueva,YujinHoshida,DerekY.Chiang,
andJosepM.Llovet
ErrolC.FriedbergandRogerA.Schultz
viii
