Review
HallmarksofCancer:TheNextGeneration
DouglasHanahan1,2,*andRobertA.Weinberg3,*
SwissInstituteforExperimentalCancerResearch(ISREC),SchoolofLifeSciences,EPFL,LausanneCH-1015,SwitzerlandDepartmentofBiochemistry&Biophysics,UCSF,SanFrancisco,CA94158,USA
3WhiteheadInstituteforBiomedicalResearch,Ludwig/MITCenterforMolecularOncology,andMITDepartmentofBiology,Cambridge,MA02142,USA
*Correspondence:dh@ep .ch(D.H.),weinberg@wi.mit.edu(R.A.W.)DOI10.1016/j.cell.2011.02.013
2The1The
LeadingEdge
Thehallmarksofcancercomprisesixbiologicalcapabilitiesacquiredduringthemultistepdevelop-mentofhumantumors.Thehallmarksconstituteanorganizingprincipleforrationalizingthecomplexitiesofneoplasticdisease.Theyincludesustainingproliferativesignaling,evadinggrowthsuppressors,resistingcelldeath,enablingreplicativeimmortality,inducingangiogenesis,andacti-vatinginvasionandmetastasis.Underlyingthesehallmarksaregenomeinstability,whichgeneratesthegeneticdiversitythatexpeditestheiracquisition,andin ammation,whichfostersmultiplehall-markfunctions.Conceptualprogressinthelastdecadehasaddedtwoemerginghallmarksofpotentialgeneralitytothislist—reprogrammingofenergymetabolismandevadingimmunedestruction.Inadditiontocancercells,tumorsexhibitanotherdimensionofcomplexity:theycontainarepertoireofrecruited,ostensiblynormalcellsthatcontributetotheacquisitionofhall-marktraitsbycreatingthe‘‘tumormicroenvironment.’’Recognitionofthewidespreadapplicabilityoftheseconceptswillincreasinglyaffectthedevelopmentofnewmeanstotreathumancancer.
INTRODUCTION
Wehaveproposedthatsixhallmarksofcancertogetherconsti-tuteanorganizingprinciplethatprovidesalogicalframeworkforunderstandingtheremarkablediversityofneoplasticdiseases(HanahanandWeinberg,2000).Implicitinourdiscussionwasthenotionthatasnormalcellsevolveprogressivelytoaneoplasticstate,theyacquireasuccessionofthesehallmarkcapabilities,andthatthemultistepprocessofhumantumorpathogenesiscouldberationalizedbytheneedofincipientcancercellstoacquirethetraitsthatenablethemtobecometumorigenicandultimatelymalignant.
Wenotedasanancillarypropositionthattumorsaremorethaninsularmassesofproliferatingcancercells.Instead,theyarecomplextissuescomposedofmultipledistinctcelltypesthatparticipateinheterotypicinteractionswithoneanother.Wede-pictedtherecruitednormalcells,whichformtumor-associatedstroma,asactiveparticipantsintumorigenesisratherthanpassivebystanders;assuch,thesestromalcellscontributetothedevelopmentandexpressionofcertainhallmarkcapabilities.Duringtheensuingdecadethisnotionhasbeensolidi edandextended,revealingthatthebiologyoftumorscannolongerbeunderstoodsimplybyenumeratingthetraitsofthecancercellsbutinsteadmustencompassthecontributionsofthe‘‘tumormicroenvironment’’totumorigenesis.
Inthecourseofremarkableprogressincancerresearchsubsequenttothispublication,newobservationshaveservedbothtoclarifyandtomodifytheoriginalformulationofthehall-markcapabilities.Inaddition,yetotherobservationshaveraisedquestionsandhighlightedmechanisticconceptsthatwerenotintegraltoouroriginalelaborationofthehallmarktraits.Moti-646Cell144,March4,2011ª2011ElsevierInc.
vatedbythesedevelopments,wenowrevisittheoriginalhall-marks,considernewonesthatmightbeincludedinthisroster,andexpanduponthefunctionalrolesandcontributionsmadebyrecruitedstromalcellstotumorbiology.
HALLMARKCAPABILITIES—CONCEPTUALPROGRESSThesixhallmarksofcancer—distinctiveandcomplementarycapabilitiesthatenabletumorgrowthandmetastaticdissemina-tion—continuetoprovideasolidfoundationforunderstandingthebiologyofcancer(Figure1;seetheSupplementalInforma-tionfordownloadableversionsofthe guresforpresentations).Inthe rstsectionofthisReview,wesummarizetheessenceofeachhallmarkasdescribedintheoriginalpresentationin2000,followedbyselectedillustrations(demarcatedbysub-headingsinitalics)oftheconceptualprogressmadeoverthepastdecadeinunderstandingtheirmechanisticunderpinnings.Insubsequentsectionsweaddressnewdevelopmentsthatbroadenthescopeoftheconceptualization,describinginturntwoenablingcharacteristicscrucialtotheacquisitionofthesixhallmarkcapabilities,twonewemerginghallmarkcapabilities,theconstitutionandsignalinginteractionsofthetumormicroen-vironmentcrucialtocancerphenotypes,andwe nallydiscussthenewfrontieroftherapeuticapplicationoftheseconcepts.SustainingProliferativeSignaling
Arguablythemostfundamentaltraitofcancercellsinvolvestheirabilitytosustainchronicproliferation.Normaltissuescarefullycontroltheproductionandreleaseofgrowth-promotingsignalsthatinstructentryintoandprogressionthroughthecellgrowth-and-divisioncycle,therebyensuringahomeostasisofcell
Hallmarks of Cancer The Next Generation中文_临床医学_医药卫生_专业资料。肿瘤十大特征 ? .cnI reiveslE 11 02 1102 ,4 hcraM ,441 lleC 646 。谢代量能...
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hallmarks of cancer the next generation 肿瘤的标志性特征。中英对照版本(英)_基础医学_医药卫生_专业资料。Hnahan与Weinberg综述肿瘤十大基本特征,中英文对照版本,...
hallmarks of cancer the next generation 肿瘤的标志性特征。中英对照版本(中)_基础医学_医药卫生_专业资料。Hnahan与Weinberg综述肿瘤十大基本特征,中英文对照版本,...
Leading Edge Review Hallmarks of Cancer: The Next Generation Douglas Hanahan1,2,* and Robert A. Weinberg3,* Swiss Institute for Experimental Cancer Researc...
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[ 9] Hanahan D,Weinberg RA. Hallmarks of cancer: the next generation[ J] . Cell, 2011 , 144 : 646-674. [ 10] White E. Deconvoluting the ...
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