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《Springer.C.J.(ed).Suicide.Gene.Therapy.Methods.and.Reviews 》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。
1、METHODSINMOLECULARMEDICINETMSuicideGeneSuicideGeneTTherapyherapyMethodsandReviewsMethodsandReviewsEditedbyEditedbyCarolineJ.SpringerCarolineJ.SpringerIntroductiontoSuicideGeneTherapy11IntroductiontotheBackground,Principles,andStateoftheArtinSuicideGeneTherapyIonNiculescu-Duvaz
2、andCarolineJ.Springer1.IntroductiontotheBackgroundandPrinciplesofSuicideGeneTherapyChemotherapyiswidelyusedwithsurgeryandradiotherapyforthetreatmentofmalignantdisease.Selectivityofmostdrugsformalignantcellsremainselusive.Unfortunately,aninsufficienttherapeuticindex,alackofspec
3、ificity,andtheemer-genceofdrug-resistantcellsubpopulationsoftenhampertheefficacyofdrugthera-pies.Despitethesignificantprogressachievedbychemotherapyinthetreatmentofdisseminatedmalignancies,theprognosisforsolidtumorsremainspoor.Anumberofspecificdifficultiesareassociatedwiththet
4、reatmentofsolidtumors,wheretheaccessofdrugstocancercellsisoftenlimitedbypoor,unequalvascularizationandareasofnecrosis.Thehistologicalheterogeneityofthecellpopulationwithinthetumorisan-othermajordrawback.Attemptstotargettherapiestotumorshavebeenaddressedbyusingprodrugsactivated
5、intumorsbyelevatedselectiveenzymesandaredescribedinChapter27.AnalternativestrategythatuseantibodiestotargettumorswithforeignenzymesthatsubsequentlyactivateprodrugsisdescribedinChapter26.Oneapproachaimedatenhancingtheselectivityofcancerchemotherapyforsolidtumorsreliesontheappli
6、cationofgenetherapytechnologies.Genetherapiesaretech-niquesformodifyingthecellulargenomefortherapeuticbenefit.Incancergenetherapy,bothmalignantandnonmalignantcellsmaybesuitabletargets.Thepossibil-ityofrenderingcancercellsmoresensitivetodrugsortoxinsbyintroducing“suicidegenes”h
7、astwoalternatives:toxingenetherapy,inwhichthegenesfortoxicproductsaretransduceddirectlyintotumorcells,andenzyme-activatingprodrugtherapy,inwhichthetransgenesencodeenzymesthatactivatespecificprodrugstocreatetoxicmetabolites.Thelatterapproach,knownassuicidegenetherapy,gene-direc
8、tedenzymeprodrugtherapy(GDEPT)(1,2),virus-directedenzymeprodr
