Enabling Characteristics - In Vitro Technologies
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A high frequency of mutations within a genome leads to genome instability. As we know cancer develops with an accumulation of mutations where cancer cell ... AllSite ProductDetails InformationPages BlogPosts EnablingCharacteristics Intheirpaper“HallmarksofCancer:TheNextGeneration”,HanahanandWeinberg(2011)reportedthattwoenablingcharacteristicsunderliethe8cancerhallmarkstheyidentified. Clickontheheadingsbelowtolearnmore Intheirpaper“HallmarksofCancer:TheNextGeneration”,HanahanandWeinberg(2011)reportedthattwoenablingcharacteristicsunderliethe8cancerhallmarkstheyidentified.Theseenablingcharacteristicsare:Genomeinstability,whichgeneratesthegeneticdiversitythatexpeditestheiracquisition,and Inflammation,whichfostersmultiplehallmarkfunctions. GenomeInstabilityandMutation > Ahighfrequencyofmutationswithinagenomeleadstogenomeinstability.Asweknowcancerdevelopswithanaccumulationofmutationswherecancercellpossessingmutationsthatsupportfastergrowth,willresultinarobusttumor.Theliteratureisclearthatmolecular-geneticanalysisadvancementsofcancercellgenomesprovidedcompellingevidenceoffunction-alteringmutationsandofongoinggenomicinstabilityduringtumorprogression.Whilethemutationsvarysignificantlybetweendifferenttumortypes,itisclearthatinstabilityofthegenomeischaracteristicofmosthumancancercells. Assuch,compromisedgenomesurveillanceisinstrumentalfortumorprogression,supportingtheaccelerationofdevelopingpremalignantcellstoaccumulatefavourablegenotypes.Genomeinstabilityisanenablingcharacteristicthatisdescribedinthehallmarkenablingreplicativeimmortality. Tumor-PromotingInflammation Duringcancer,NFKBisactivatedinimmunecellstoultimatelyattractmoreimmunecellsintothetumor.ThemainimmunecellsaretheTumorAssociatedMacrophages(TAMs)thatarefoundinmostmalignanttumors,wheretheycancompriseupto50percentofthecelltumormass.TAMsassistcancercellstobypasssomeoftheanti-cancerdefencemechanismstosupporttumorgrowththroughfourmainmechanisms.Supplyofgrowthfactors(EGF,FGF)andcytokines(IL-6,TNFα)asnotedinthehallmarkself-sufficiencyingrowthsignals. TAMssecreteVEGFANDPDGFintothetumormicroenvironmenttopromoteangiogenesisthroughthehypoxiaresponsepathwayaspresentedinthehallmarksustainedangiogenesis. TAMssecretematrixmetalloproteasesleadingtoinvasionandmetastasesdescribedinthehallmark activatinginvasionandmetastasis. TAMssupportthetumor’sabilitytoevadetheimmunesystemthroughtheproductionofimmunosuppressivemoleculesthatneutralizetheimmunesystems’abilitytokillcancercellsaspresentedinthehallmarkoncancerimmunotherapy
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