Bacteria-Directed Enzyme Prodrug Therapy, A NoveleAnd Reliable Prospective Method For Targeted Cancer Therapy

Despitee thee largee numbere ofe variouse anti-cancere drugse one thee market,e cancere remainse onee ofe themoste deadlye diseasese worldwidee withe thee numbere ofe casese steadilye increasing.e Amonge thee mostpromising,emoreerecentedevelopmentseareedirectedeenzymeeprodrugetherapies.eAlledirectedeenzymeprodrugetherapieseoperateewithetheesameebasiceconcept:eaenontoxiceprodrugeiseconvertedeintoeaetoxicdruge insidee ofe cellse whiche weree transformede withe ae genee constructe (GDEPT)e ore bacteriae (BDEPT)encodinge thee enzymee needede fore thee prodrug/druge conversione ore antibodye (ADEPT)e ase antibodyprodrug/druge convertinge enzymee fusione proteins.e Recently,e severale generae ofe bacteriae havee beenshownetoespecificallyeaccumulateeandereplicateewithinetumors,eincludingeClostridium,eSalmonella,Bifidobacterium,e Listeriae ande E.e coli.e Thesee bacteriae cane causee cancere celle deathe bye competinge fornutrientseand/orebyesecretingetoxicebacterialeproducts.eIneBDEPTemethod,ethatehaseevenebeeneusedeinpilote trialse fore refractorye cancere patients,e somee ofe thesee bacteriae aree utilizede ase specifice genedeliverye vehiclese fore selectivee enzymee activatione ofe prodrugse ate thee tumore microenvironmente toincreaseetreatmentespecificity.eRecently,eSalmonellaeexpressingecarboxypeptidaseeG2,eEscherichiacolie expressinge βe -glucuronidasee (βG),e Salmonellae expressinge herpese simplexe viruse thymidinekinase,e Salmonellae expressinge E.e colie cytosinee deaminasee (CD)e ande Listeriae expressinge purinenucleosidee phosphorylasee (PNP)e havee beene showne toe generatee potente ande selectivee antitumoractivitye bye convertinge systemicallye administerede prodrugse toe activee anticancere agentse ine varioustypese ofe tumors,e whilee minimizinge exposuree ofe normale tissuese toe activee drugs.e Bacteria-directedenzymeeprodrugetherapye(BDEPT)eiseaepromisingetherapeuticeapproacheforetreatmenteofesomeesolidtumors.eOptimizationeandeimprovementeofetheeselectedeprospectiveemodeletypeeofeBDEPTewouldehelptoeimproveetheedevelopmenteofebacterial-mediatedecanceretreatmenteandedrugedeliveryesystemseandtheiresuccessfuleapplicationseinefutureeclinicaletrials.