药学研究进展论文

Theprogressofresearchwithantitumordrug[abstract]:Nearly50yearsofresearchanddevelopmentofanticancerdrugshasmadeconsiderableprogressincancerchemotherapy,particularlyitenablespatientswithhematologicmalignanciessignificantlyprolongsurvivaltime,Butaseriousthreattohumanlifeandhealthaccountedforover90%ofmalignantsolidtumorshasnotyetreachedasatisfactoryeffect.Halfofcancerpatientsarestillnoresponseorresistancetotreatmentandeventuallyleadtotreatmentfailure,sothediscoveryanddevelopmentofnewanticancerdrugsbypharmaceuticalcompaniesisstillverydifficulttobefacedwiththechallengeoflong-termmission[1].Thischapterprovidessomebriefabouthotareasandthelatestdevelopments.[keyword]:Antineoplastic,Traditionalanticancerdrugs,Newanticancerdrugs1.Traditionalanticancerdrugs1.1Classification:Accordingtothechemicalstructureandsourcesofdrugsitincludesalkylatingantineoplasticagents(Cyclophosphamide),Antimetabolite(Fluorouracil),Antibiotics(doxorubicin.etc.),plantalkaloids(vincristine),hormones.1.2Cytotoxicanticancermechanismofaction:①Interferingnucleicacidbiosynthesis②thedrugthatdirectlyaffectstheDNAstructureandfunction③thedrugthatinterfereswiththeprocessoftranscriptionandRNAsynthesis④thedrugthatinterfereswithproteinsynthesisandfunction1.3Feature:Currentlyconsiderableperiodoftimeorintraditionalcytotoxiccancertherapydrugswillcontinuetobethesubjectofmajordrawbackofthesedrugsispoorsolidtumorefficacy,sideeffects,easytoproducedrugresistance.Inrecentyears,throughthecancerpatientsduringchemotherapyadversereactionsanalysisconcludedthatmostoftheexistingchemotherapydrugsisnotstrongselectivityininhibitingorkillingtumorcellswhilenormalcells,especiallyproliferativecells(suchasbonemarrow,hairfollicles)alsoinhibitcytotoxicity.Thus,inthenormaltherapeuticdosechemotherapydrugswhenyoucanmakethebodyproduceadversereactions2.Newanticancerdrugs2.1MoleculartargetedanticancerdrugsAtthemolecularlevel,consideringthedifferencebetweennormalcellsandthetumorcells,directedtothetumorcells’sometargets,effectivelykilltumorcellswhileminimizetheimpactonnormalcells,Thishighselectiveeffectsignificantlyreducedtoxicity,increasedpatienttoleranceandcompliance,Theemergenceofmoleculartargeteddrugstoovercomethetraditionalpoorselectivityofcytotoxicdrugs,sideeffects,easytoproducedrugresistanceandothershortcomings[2],Alargenumberoftargeteddrugshavebeenputintoclinical,includingcellsignalingmoleculesGoinhibitors,angiogenesisinhibitors,tumordifferentiationinducedbydrugs.2.1.1CellularsignaltransductionmoleculeinhibitorsManydifferentiationfactorsignaltransductionduringcelldifferentiationcontainsproteinkinasefamily.Overexpressionofthisproteinkinasecaninducetumor.Sincetheseproteinkinasegenemutationorrearrangementresultinginsignaltransductionprocessesobstaclesandanomalies,whichbyaffectingcellgrowth,differentiation,metabolismandbiologicalbehaviorandcausetumors.Currently,anumberofproteinkinaseinhibitorsandthedifferentproteinkinaseATPbindingsiteofasmallmoleculetherapeuticagenthasbeeninclinicalstudies.Thesenewdrugsaretargetedinhibitionofcellcyclekinases,suchastyrosinekinases,proteinkinaseC,proteinkinaseAandsoon.Currently,thenewcellularsignaltransductioninhibitorwasdevelopedfortargetedcancertherapyresearchfocus,therearesomeproteinkinaseinhibitorsarebeingdeveloped,includingtheWesttoNeeb,axitinib,etc.[3],inrecentyears,thereareavarietyofcellularsignaltransductionmoleculeinhibitorslisted.2.1.2AngiogenesisinhibitorsAngiogenesishasacrucialroleintumorgrowthandmetastasis.SinceFoikman[4]proposedtheconceptofangiogenesisinthe1970s,thentheinhibitionofangiogenesishasalsobeenaresearchfocus,tumorangiogenesisbybothpositiveandnegativeregulatoryfactorcontrol.Andvascularendothelialgrowthfactorreceptortyrosinekinaseintumorangiogenesisandtumorbloodvesselstomaintainexistinghasitsimportantroleinblockingtumorangiogenesisisanimportanttarget.Avastinthatiscurrentlyrepresentedinclinicaltumorangiogenesisinhibitorshasbeenwidelyrecognized,includingChinathereare28countrieshavingratifiedtheclassinhibitorsactontheclinicaltreatmentofcancer[5].Recentstudieshavefoundthat,AngiostatinandEndostatincanalsoplayahighlyeffectiveanti-tumoreffectthroughantagonizeangiogenicfactors.2.1.3TumordifferentiationinducedbydrugsEvilcancerisadisorderofcelldifferentiation,celldifferentiationdisordercausedbythisspecificgenesincertainconditionsisreversible.Inducingdrugsbyaffectingcelldifferentiationgenecertaindecisionstofurtherdifferentiation,itsvaluecanbereversed,invasion,andmetastasisofmalignantmanifestations,makingnormalornearnormalcells,thusbecominganewapproachtocancercontrol.Currently,themaindrugsincludetumornecrosisfactor,vitaminAacidcompounds,choleratoxinandsoon.Tumornecrosisfactorcaninduceapoptosisincertaintumorcells,inhibitcancercellproliferation,butalsoactontheendothelialcells,thetumorvascularinjuryorthrombosis,leadingtotumornecrosis.VictoriaAacidcompoundscanpromoteapoptosisoftumorcells,inductionofdifferentiationandinhibitionofthegrowth,currentlyitmainlyusedintheclinicaltreatmentofleukemia.CholeratoxincaninhibitcellPI3K/PKBpathwayactivatedkinaseCSK-