Post on 30-May-2020
OBJECTIVES1. Listthemajorhallmarksofcancer
2. Relatespecificgenes/proteinstoindividualhallmarks
3. Explainhowhallmarksofcancerleadtocancerdevelopment
Source:www.123rf.com
CaseStudy• 60yearoldfemale
• Previouslytreatedforbreastcancer(5yearsprior);norecurrence
• Presentswithpersistentcough,shortnessofbreath,fatigue
• X-rayrevealssmallmassinleftlung
• Abiopsyisperformed
think-discuss-shareAphysicianmeetswiththispatient.Whatisthefirst questionsheasksaboutthepatient’slifestyle?
www.lung.org
www.lung.org
brainstormingApathologistanalyzesthebiopsysample.Whatdoesshelookfor?,i.e.Whatinformationisgainedfromtheanalysisofthebiopsy?
www.lung.org
TYPESOFLUNGCANCER
Biopsyresultsindicatethatpatienthasametastatictumorofbreastcancerorigininlung.Tumorisacarcinoma.
Biopsyresultsindicatethatpatienthasametastatictumorofbreastcancerorigininlung.Tumorisacarcinoma.
QUESTION – Whatchangesoccurredtoabreastepithelialcellthatledtotheformationofametastatictumorinthelung?
DouglasHanahan
RobertWeinberg
Hanahan andWeinberg(2000)Cell,100:57– 70.
CELLDIVISION
GROWTHFACTOR(GF)
RECEPTOR
INTRACELLULARSIGNALINGPATHWAY
CELLDIVISION
GROWTHFACTOR(GF)
RECEPTOR
INTRACELLULARSIGNALINGPATHWAY
Ras
CELLDIVISION
RECEPTOR
INTRACELLULARSIGNALINGPATHWAY
HyperactiveMutantRas inCancers
Ras
GROWTHFACTOR(GF)
INTRACELLULARSIGNALINGPATHWAY
CELLDIVISION
AmplifiedEGFReceptorsinCancer
Source:Cheng,L.etal.(2012)ModernPathology,25:347– 369.
CLASSESOFLUNGADENOCARCINOMA
Ras
www.tarceva.com
www.lifewithlungcancer.org
TARCEVA – ADRUGWHICHTARGETSEGFRECEPTORINLUNGCANCER
Hanahan andWeinberg(2000)Cell,100:57– 70.
EUKARYOTICCELLCYCLE
G0
RECEPTOR
INTRACELLULARSIGNALINGPATHWAY
Rb
RECEPTOR
INTRACELLULARSIGNALINGPATHWAY
Rb-P
CELLDIVISION
GROWTHFACTOR(GF)
ModifiedandInactiveRb
RECEPTOR
INTRACELLULARSIGNALINGPATHWAY
Rb
CELLDIVISION
InactiveMutantRb
inCancer
p53’sNORMALROLEISTOINHIBITCELLDIVISIONINRESPONSETOCELLULARSTRESSESLIKEDNADAMAGE
TUMORCELLSLACKINGp53DONOT ARRESTCELLCYCLE
Source:MolecularBiologyoftheCell,Alberts etal.
Hanahan andWeinberg(2000)Cell,100:57– 70.
APOPTOSIS– PROGRAMMEDCELLDEATH
Source:MolecularBiologyoftheCell,Alberts etal.
CELLDIVISION
INSULIN-LIKEGROWTHFACTOR(IGF-1)
IGF-1R
INTRACELLULARSIGNALINGPATHWAY
Ras
CELLSURVIVAL
CELLDIVISION
INSULIN-LIKEGROWTHFACTOR(IGF-1)
IGF-1R
INTRACELLULARSIGNALINGPATHWAY
Ras
CELLSURVIVAL
SOMECANCERCELLSUPREGULATECELLSURVIVALPATHWAYSTOEVADEAPOPTOSIS
Hanahan andWeinberg(2000)Cell,100:57– 70.
TELOMERES ARECHROMOSOMEENDS
TELOMERESAREMADEBYTELOMERASE EARLYINDEVELOPMENT;THENTELOMERASEACTIVITYISNORMALLYTURNEDOFF
TELOMERESSHORTENWITHEACHCELLDIVISION,ULTIMATELYLEADINGTOSENESCENCE
CANCERCELLSREACTIVATE TELOMERASE
Biopsyresultsindicatethatpatienthasametastatictumorofbreastcancerorigininlung.Tumorisacarcinoma.
Hanahan andWeinberg(2000)Cell,100:57– 70.
Theformationofnewbloodvesselsfrompre-existingbloodvessels.
VEGF=VascularEndothelialGrowthFactor
Biopsyresultsindicatethatpatienthasametastatictumorofbreastcancerorigininlung.Tumorisacarcinoma.
Hanahan andWeinberg(2000)Cell,100:57– 70.
brainstormingWhathastohappentoabreastcarcinomacelltoallowittometastasizetothelung?
PRIMARYBREASTCARCINOMA
METASTATICTUMORINLUNG
METASTASIS
CELLSOFPRIMARYTUMORREDUCEEXPRESSIONOFINTERCELLULARCONNECTIONS(E-CADHERINS)ANDCONNECTIONSTOTHEEXTRACELLULARMATRIX(INTEGRINS)TOALLOWMETASTASIS
Hanahan andWeinberg(2000)Cell,100:57– 70.
CANCERDEVELOPMENTISAMULTI-STEPPROCESS.
INDIVIDUALSTEPSCANOCCURISDIFFERENTORDER.
Ras,EGFReceptor
Rb,p53
IGF-1,IGF-1R
Telomerase
VEGF
E-cadherin
THEHALLMARKSOFCANCER
Youshouldbeableto...1. Listthemajorhallmarksofcancer
2. Relatespecificgenes/proteinstoindividualhallmarks
3. Explainhowhallmarksofcancerleadtocancerdevelopment