Gene therapy against brain cancer Promising results for “targeted” treatments against glioblastoma May 13, 2016 A team from the International School for Advanced Studies (SISSA) in Trieste has obtained very promising results by applying gene therapy to glioblastoma. Tests in vitro and in vivo on mice provided very clear-cut results, and modelling demonstrates that the treatment targets at least six different points of tumour metabolism. Gene therapy, a technique that selectively attacks a tumour, might provide hope in the fight against this type of deadly cancer, for which surgery is practically impossible and chemo- and radiotherapy are ineffective against very aggressive recurrences. The study was published in the journal Oncotarget.
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Genetherapyagainstbraincancer
Promisingresultsfor“targeted”treatmentsagainstglioblastomaMay13,2016AteamfromtheInternationalSchoolforAdvancedStudies(SISSA)inTriestehasobtainedverypromisingresultsbyapplyinggenetherapytoglioblastoma.Testsinvitroandinvivoonmiceprovidedveryclear-cutresults,andmodellingdemonstratesthatthetreatmenttargetsatleastsixdifferentpointsoftumourmetabolism.Genetherapy,atechniquethatselectivelyattacksatumour,mightprovidehopeinthefightagainstthistypeofdeadlycancer,forwhichsurgeryispracticallyimpossibleandchemo-andradiotherapyareineffectiveagainstveryaggressiverecurrences.ThestudywaspublishedinthejournalOncotarget.
Onlyafewdaysago,thepress(especiallyinEnglish-speakingcountries)enthusiasticallyannouncedthepublicationofastudythatdescribedingreatdetailthegeneticsofbreastcancer,adiscoverythataccordingtomanymarksabreakthroughinthebattleagainstthiscancer.Thiskindofnewsconfirmstheimpressionthatinthenearfuturethewaragainstcancerwillbefoughtonthebattlefieldsofgenetics.Italytoo,isworkingonthisfront.AtSISSA,forexample,whereAntonelloMallamaciandhisgrouphavejustpublishedhighlypromisingresultsontheapplicationofgenetherapyagainstglioblastomas,afamilyofbraintumoursamongthemostcommonandaggressive.Adiagnosisofglioblastomaisliterallyequaltoaveryimminentdeathsentence:“surgeryisrarelycurative,asthesetumoursinsinuatethemselvesinhealthytissues,andalsochemo-andradiotherapyhavelittleeffectiveness.Inashortwhile,veryaggressiverecurrencesdevelopandthatmarkstheend”explainsAntonelloMallamaci,SISSAprofessorwhoalsocollaborateswiththeTelethonFoundation.“Ourapproachisradicallydifferent:weintroduceanadditionalcopyofagivengeneintothetumourcellssoastoimpairtheirreproductivecapacityandleadthemtosuicide”.TheideaforthisstudycametoMallamaci–whoisnotanoncologist–afteryearsofcloseinvestigationofaparticulargenecalledEmx2.Oneofthecharacteristicsofthisgene,explainsthescientist,istoinhibitproliferationofastrocytesduringembryonicgrowth.Glialcells,includingastrocytes,arepartofthenervoussystem,wheretheynourishandprotectneuronsandfinelyregulatetheirfunction.“Weknowthatduringtheearlystagesofdevelopmentofthenervoussystemonlyneuronsgrow,whereasglialcellsonlystarttoproliferatewhenneuronalgrowthispracticallycomplete”,explainsCarmenFalcone,SISSAresearchscientistandfirstauthorofthepaper.“InourpreviousstudieswediscoveredthatEmx2isexpressedatveryhighlevelsduringtheneuronalgenerationphase,whereasitsactiondeclinesdramaticallywhentheglialcellsstarttogrow.Sothegenekeepsastrocytegrowthincheckuptoacertainpoint”.Ifitcanblockastrocytes,whynottryanduseittoblockglioblastomas?“Thesetumourssharemanyfeatureswithastroglia”commentsMallamaci,“hencetheideatousethemtoouradvantage.WiththecontributionofISTinGenoa,whichsupplieduswithculturesofvarioustypesofglioblastoma,westarteddoingsomeinvitrotests”.Andthesetestswent“beyondourrosiestexpectations”,explainFalconeandMallamaci:“innearlyallofthesamples,thetumourtissueliterallycollapsedinlessthanaweek.”.Atthispointthestudycontinuedintwodirections.Theteamfirstmodelledinvitrothemolecularmechanismsinterveningbetweenwhenthetherapeuticgeneis“switchedon”andthefinal
effect,findingthatthegeneattackstumourmetabolismatnolessthansixpoints,aresultdefinedas“veryrobust”bytheresearchers.ATrojanhorseinsidethetumourAftertheinvitrostudies,thegroupstarteditsfirstinvivoexperimentsonmice,adoptingalldueprecautionstopreventunacceptablesufferingoftheanimals.“So,topreventdamagetothehealthycells,neuronsandastrocytes,weselectedaspecific‘promotor’,apieceofDNAthatcausesthetherapeuticgenetobecomeactivatedonlyintumourcells,withoutattackingtheothercells,andwereplicatedthesameresultasseeninthefirstinvitrotests”.Genetherapyisbasedontheinsertionofadhocgenesintoahostcell’sgenomesothatthesegenescanfunctioninsidethecellbyborrowingitsgeneticmachinery.Howisabitofgeneticcodeaddedtoalivingcell?Scientistsusethemechanismsnaturallyadoptedbyviruses.Virusesarestrangeentities:althoughtheyhavetheirowngenome,theyarenotabletoduplicate,andreproduce,bythemselves.Forthisreasontheysneakintocells,andinserttheirownDNAintothehostgenome,sothatthecellstartsworkingforthembyduplicatingtheirgenesaswellandformingotherviruses.“Bymakingthevirusharmless,thatis,byemptyingtheshellcontainingitsgenomeandfillingitwiththerapeuticgenes,wecanaddnewgenes,orenhancedversionsofendogenousgenes,tothehostcell”,explainsFalcone.SothatispreciselywhatMallamaciandcolleaguesdid:theyintroducedaparticularlyactiveversionofEmx2intothetumourcells.TheresultssofarhavebeenunequivocalandhavedemonstratedthatEmx2isabletokillthecellsofatleastfourdifferenttypesofglioblastoma,bothinvitroandinvivoinrodents,withoutdamagingthehealthycellsofnervoussystem.Sincetheyalsoobservedthatthetreatmenttargetedmaypointsofthetumourprocess,therearegoodchancesofeffectivelycontrastingthedevelopmentofaggressiverecurrences.“Forthesetoform,therehastobeaprocessofselectionofthestrongesttumourcells.Bytargetingthematavarietyofdifferentpoints,weraisethestandardsinthisselectionprocessand–hopefully–wepreventtherecurrences”,concludesMallamaci.“Nowweplantoextendtheinvivoteststootherglioblastomas.Withalotofhardworkandabitofluckwehopethatinafewyears’timeallthiscantranslateintoatangiblebenefitfortheunfortunatepatientsafflictedbythisdisease”.USEFULLINKS:
• Informationonglioblastoma:http://goo.gl/HKrlzE• OriginalpaperonOncotarget:http://goo.gl/2O96UI
IMAGE:
• Glioblastomacells–Credits:SISSA
Contact:
Pressoffice:[email protected]:(+39)0403787644|(+39)366-3677586viaBonomea,26534136TriesteMoreinformationaboutSISSA:www.sissa.it
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