hallmarks of cancer - lehigh universityinbios10/pdf/2017/kuchka... · 2017-09-11 · 3.explain how...
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OBJECTIVES1. Listthemajorhallmarksofcancer
2. Relatespecificgenes/proteinstoindividualhallmarks
3. Explainhowhallmarksofcancerleadtocancerdevelopment
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Source:www.123rf.com
CaseStudy• 60yearoldfemale
• Previouslytreatedforbreastcancer(5yearsprior);norecurrence
• Presentswithpersistentcough,shortnessofbreath,fatigue
• X-rayrevealssmallmassinleftlung
• Abiopsyisperformed
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think-discuss-shareAphysicianmeetswiththispatient.Whatisthefirst questionsheasksaboutthepatient’slifestyle?
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www.lung.org
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www.lung.org
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brainstormingApathologistanalyzesthebiopsysample.Whatdoesshelookfor?,i.e.Whatinformationisgainedfromtheanalysisofthebiopsy?
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www.lung.org
TYPESOFLUNGCANCER
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Biopsyresultsindicatethatpatienthasametastatictumorofbreastcancerorigininlung.Tumorisacarcinoma.
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Biopsyresultsindicatethatpatienthasametastatictumorofbreastcancerorigininlung.Tumorisacarcinoma.
QUESTION – Whatchangesoccurredtoabreastepithelialcellthatledtotheformationofametastatictumorinthelung?
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DouglasHanahan
RobertWeinberg
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Hanahan andWeinberg(2000)Cell,100:57– 70.
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CELLDIVISION
GROWTHFACTOR(GF)
RECEPTOR
INTRACELLULARSIGNALINGPATHWAY
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CELLDIVISION
GROWTHFACTOR(GF)
RECEPTOR
INTRACELLULARSIGNALINGPATHWAY
Ras
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CELLDIVISION
RECEPTOR
INTRACELLULARSIGNALINGPATHWAY
HyperactiveMutantRas inCancers
Ras
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GROWTHFACTOR(GF)
INTRACELLULARSIGNALINGPATHWAY
CELLDIVISION
AmplifiedEGFReceptorsinCancer
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Source:Cheng,L.etal.(2012)ModernPathology,25:347– 369.
CLASSESOFLUNGADENOCARCINOMA
Ras
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www.tarceva.com
www.lifewithlungcancer.org
TARCEVA – ADRUGWHICHTARGETSEGFRECEPTORINLUNGCANCER
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Hanahan andWeinberg(2000)Cell,100:57– 70.
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EUKARYOTICCELLCYCLE
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G0
RECEPTOR
INTRACELLULARSIGNALINGPATHWAY
Rb
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RECEPTOR
INTRACELLULARSIGNALINGPATHWAY
Rb-P
CELLDIVISION
GROWTHFACTOR(GF)
ModifiedandInactiveRb
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RECEPTOR
INTRACELLULARSIGNALINGPATHWAY
Rb
CELLDIVISION
InactiveMutantRb
inCancer
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p53’sNORMALROLEISTOINHIBITCELLDIVISIONINRESPONSETOCELLULARSTRESSESLIKEDNADAMAGE
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TUMORCELLSLACKINGp53DONOT ARRESTCELLCYCLE
Source:MolecularBiologyoftheCell,Alberts etal.
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Hanahan andWeinberg(2000)Cell,100:57– 70.
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APOPTOSIS– PROGRAMMEDCELLDEATH
Source:MolecularBiologyoftheCell,Alberts etal.
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CELLDIVISION
INSULIN-LIKEGROWTHFACTOR(IGF-1)
IGF-1R
INTRACELLULARSIGNALINGPATHWAY
Ras
CELLSURVIVAL
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CELLDIVISION
INSULIN-LIKEGROWTHFACTOR(IGF-1)
IGF-1R
INTRACELLULARSIGNALINGPATHWAY
Ras
CELLSURVIVAL
SOMECANCERCELLSUPREGULATECELLSURVIVALPATHWAYSTOEVADEAPOPTOSIS
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Hanahan andWeinberg(2000)Cell,100:57– 70.
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TELOMERES ARECHROMOSOMEENDS
TELOMERESAREMADEBYTELOMERASE EARLYINDEVELOPMENT;THENTELOMERASEACTIVITYISNORMALLYTURNEDOFF
TELOMERESSHORTENWITHEACHCELLDIVISION,ULTIMATELYLEADINGTOSENESCENCE
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CANCERCELLSREACTIVATE TELOMERASE
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Biopsyresultsindicatethatpatienthasametastatictumorofbreastcancerorigininlung.Tumorisacarcinoma.
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Hanahan andWeinberg(2000)Cell,100:57– 70.
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Theformationofnewbloodvesselsfrompre-existingbloodvessels.
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VEGF=VascularEndothelialGrowthFactor
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Biopsyresultsindicatethatpatienthasametastatictumorofbreastcancerorigininlung.Tumorisacarcinoma.
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Hanahan andWeinberg(2000)Cell,100:57– 70.
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brainstormingWhathastohappentoabreastcarcinomacelltoallowittometastasizetothelung?
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PRIMARYBREASTCARCINOMA
METASTATICTUMORINLUNG
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METASTASIS
CELLSOFPRIMARYTUMORREDUCEEXPRESSIONOFINTERCELLULARCONNECTIONS(E-CADHERINS)ANDCONNECTIONSTOTHEEXTRACELLULARMATRIX(INTEGRINS)TOALLOWMETASTASIS
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Hanahan andWeinberg(2000)Cell,100:57– 70.
CANCERDEVELOPMENTISAMULTI-STEPPROCESS.
INDIVIDUALSTEPSCANOCCURISDIFFERENTORDER.
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Ras,EGFReceptor
Rb,p53
IGF-1,IGF-1R
Telomerase
VEGF
E-cadherin
THEHALLMARKSOFCANCER
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Youshouldbeableto...1. Listthemajorhallmarksofcancer
2. Relatespecificgenes/proteinstoindividualhallmarks
3. Explainhowhallmarksofcancerleadtocancerdevelopment