InnovativeTreatmentsForCervicalCancer
Cervicalcancerisoneofthemostcommongynecologicalmalignancies, secondonlytobreastcancerinincidence.AccordingtotheWorldHealth Organization(WHO),therewere604,000newcasesofcervical cancerworldwidein2020,andabout340,000womendiedfromthedisease. Cervicalcancerisoftencausedbythehumanpapillomavirus(HPV),andother riskfactors,suchasHIVinfectionandsmoking,canalsoaffecttheriskof cervicalcancerinawomaninfectedwithHPVInrecentyears,withthe improvementofpublicawarenessofpreventionandthepopularizationofHPV vaccination,thespreadofHPVvirusandthecorrespondingincidenceof cervicalcancerhavebeeneffectivelycontrolled.
AccordingtothedatareleasedbytheJournaloftheNationalCancerCenter, theincidenceofcervicalcancerranksfifthamongfemalemalignanttumorsin China.Foradvancedcervicalcancer,theeffectofchemotherapyisrelatively poor,andmoreeffectivetreatmentsareneededInrecentyears,the emergenceoftargetedtherapyandimmunotherapyhasbroughtnewhopeto patientswithadvancedcervicalcancerCurrently,twotargetedtherapiesand twoimmunotherapieshavebeenapprovedclinicallyforthetreatmentof advancedcervicalcancer
TargetedDrugsforCervicalCancer
Targeteddrugsrefertodrugsthatspecificallytargetproteinsoncervical cancercellsthathelpthemgrow,spread,orlivelonger,andexertanti-cancer effectsbydestroyingcancercellsorslowingdowntheirgrowth.Becauseof theirdifferentmodesofaction,theyalsohaveverydifferentsideeffectsfrom chemotherapydrugs.
1.Drugstargetingtumorangiogenesis-angiogenesisinhibitors
Intheprocessoftumorgrowth,newbloodvesselsneedtobecontinuously formedtoobtainthenutrientsneededforgrowthVascularendothelialgrowth factor(VEGF)isakeyproteinthatcanhelptumorsformnewbloodvessels.
TargeteddrugsagainstVEGFproteincanpreventtheformationoftumornew bloodvesselsbyinhibitingtheproteinfunctionofVEGFandrelatedsignaling pathways,therebyeffectivelycurbingtumorgrowth
TheVEGF-targeteddrugcommonlyusedclinicallyinthetreatmentofcervical cancerismainlybevacizumab(tradename:Avastin),whichisthefirsttargeted drugapprovedforcervicalcancerBevacizumabisamonoclonalantibodythat isoftenusedwithchemotherapydrugs,andifpatientsrespondtothis combinationregimen,theycanstopchemotherapyandbetreatedwith bevacizumabaloneuntilthecancerreturns
In2014,theFDAapprovedbevacizumab(Avastin)incombinationwith chemotherapyforthetreatmentofpatientswithrecurrentoradvanced (metastatic)cervicalcancerTheGOG240studyshowedthatcombined therapywithtargeteddrugbevacizumabcansignificantlyimprovetheoverall survivalofpatientswithcervicalcancerwithoutcausingadeclineinthequality oflifeofpatients.Atpresent,bevacizumabhasbeenrecommendedby theNationalComprehensiveCancerNetwork(NCCN)guidelinesasthefirst choiceforthetreatmentofmetastaticcervicalcancer.Theindicationofthe drugforcervicalcancerhasalsobeenapprovedbytheNationalMedical ProductsAdministration(NMPA).
BevacizumabmayhavedifferentsideeffectsthanchemotherapydrugsSome ofthemorecommonsideeffectsmayincludeproteinuria,highbloodpressure, proteinuria,arterialandvenousthromboembolism,cardiovasculartoxicity, hemorrhage,intestinalperforationandsoon
2.Antibodydrugconjugates
Antibodydrugconjugates(ADC)isadrugthatcombinesachemotherapydrug withamonoclonalantibody.Itbindstoaspecificproteinonacancercelland deliversthechemotherapydrugtothecancercell,whereitcanbetargeted Currently,tisotumabvedotin(Tivdak)isanADCforthetreatmentof cervicalcancerThedrugtargetsatissuefactor(TF)proteinoncancercells anddeliversthecytotoxicdrugMMAEdirectlyintocancercellsbyattachingto theTFproteinItdisruptsthemicrotubulenetworkthatdividescancercells, leadingtocellcyclearrestandcelldeath.In2021,theFDAgranted acceleratedmarketingapprovalforTivdaktotreatadultpatientswithrecurrent ormetastaticcervicalcancerwhosediseasehasprogressedduringorafter chemotherapyItisworthmentioningthatTivdakisthefirstandcurrentlyonly approvedADCdrugforcervicalcancerThedrugisstillbeingapprovedfor saleinChina.
DatafromthepivotalPhaseIIinnovaTV204studyshowthattisotumab vedotinissignificantlyeffectiveasamonotherapytoprovideclinically significantandlong-lastingobjectiveremissioninpatientswithcervicalcancer:
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https://ushuatengscicom
Theoverallresponserate(ORR)was24%,themediandurationofresponse (DOR)was8.3months,andthesafetywascontrollable.
CommonsideeffectsofTivdakmayincludefeelingtired,nausea,hairloss, vomiting,bleeding,diarrhea,rash,andnervedamage(peripheralneuropathy) Othercommonsideeffectsmayincludeabnormalitiesinbloodindicators,such aslowredbloodcellcount(anemia),lowwhitebloodcellcount,andabnormal kidneyfunction.Inaddition,patientstreatedwithTivdakmayalsoexperience dryeyes,changesinvision,decreasedvision,orcornealulcers,andpatients shouldhaveregulareyeexamswhileusingthismedication.
ImmunotherapyforCervicalCancer
Immunotherapyworksbyusingsubstancesmadebythebodyorina laboratorytoboosttheimmunesystemandhelpthebodyfindanddestroy cancercells.Immunotherapyusuallyworksonspecificproteinsinvolvedinthe actionoftheimmunesystemtoenhancetheimmuneresponseSome immunotherapydrugs(suchasmonoclonalantibodies)workbyblocking specificproteinsoncancercellssothattheycannotgrow,andaretherefore sometimesconsideredtobetargetedtherapiesImmunotherapiesclinically usedtotreatcervicalcancerworkprimarilybyinhibitingimmunecheckpoints, proteinsonimmunecellsthatcontroltheinitiationorshutdownoftheimmune response,andcancercellssometimesusethesecheckpointproteinstoavoid
HuatengPharma https://ushuatengscicom beingattackedbytheimmunesystem,soinnovativedrugstargetingthese proteinscanbeusedincancertreatment.
1.Pembrolizumab(Keytruda)
Theimmunecheckpointinhibitorthatcanbeusedinthetreatmentofcervical cancerispembrolizumab(Keytruda),whichtargetsPD-1.ByblockingPD-1, itsignificantlybooststheimmunesystem'simmuneresponseagainstcancer cells,whichcanshrinktumorsinsizeorslowtheirgrowth.In2018,Keytruda receivedacceleratedapprovalfromtheUSFDAforthesecond-linetreatment ofpatientswithrecurrentormetastaticcervicalcancer,becomingthefirstPD-1 immunotherapyapprovedforthetreatmentofadvancedcervicalcancer StudiesinrecentyearshaveconfirmedthatKeytrudaalsohasexcellent performanceinthefieldoffirst-linetreatmentofcervicalcancer,andis expectedtobecomeafirst-linetreatmentoptionforpatientswithadvanced cervicalcancer,significantlyimprovingtheprognosisofpatientswithcervical cancer[3].
2.Cemiplimab(Libtayo)
InNovember2022,theEuropeanCommission(EC)hasapproved cemiplimab(Libtayo)asmonotherapyforthetreatmentofadultpatientswith recurrentormetastaticcervicalcancerwhosediseasehasprogressedduring orafterplatinum-basedchemotherapy
Theapprovalismainlybasedontheresultsofthephase3clinical trial,EMPOWER-Cervical.Theresultsofthestudyshowedthatcompared withthechemotherapygroup,patientstreatedwithLibtayohadsignificantly improvedoverallsurvival(OS),progression-freesurvival(PFS)andobjective responserate(ORR)[5]Specificdataareasfollows:
Amongallcervicalcancerpatients,Libtayoreducedtheriskofdeathby31%, withamediansurvivalof12.0monthsintheLibtayotreatmentgroupand8.5 monthsinthechemotherapygroup;a25%reductionintheriskofdisease progression;andamorethandoubledORR(16.4%vs6.3%);themedian durationofresponse(DOR)wassignificantlyprolonged(164monthsvs69 months).
Inpatientswithsquamouscellcarcinoma(SCC),Libtayoreducedtheriskof deathby27%,withamediansurvivalof11.1monthsintheLibtayotreatment groupand88monthsinthechemotherapygroup;a29%reductionintherisk ofdiseaseprogression;andamorethandoublingoftheORR(17.6%vs 67%)
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Inpatientswithadenocarcinoma(AC),Libtayoreducedtheriskofdeathby 44%,withamediansurvivalof13.3monthsintheLibtayotreatmentgroupand 70monthsinthechemotherapygroup;a9%reductionintheriskofdisease progression;andanearly3-foldincreaseinORR(12%vs4%) SurvivalwithCemiplimabinRecurrentCervicalCancer
HuatengPharma https://ushuatengscicom Possiblesideeffectsofimmunotherapydrugsincludefatigue,fever,nausea, headache,rash,lossofappetite,constipation,joint/musclepain,anddiarrhea. Becausethesedrugsworkbyremovingthe"brake"moleculesofthebody's immunesystem,theymaycausetheimmunesystemtoattackotherpartsof thebody,causingseriousandevenlife-threateningconditionsinavarietyof organs,suchasthelungs,intestines,liver,hormone-makingglands,kidneys, andmore.Butingeneral,it'srare.
Conclusion
Inrecentyears,withthedevelopmentofnewtherapeuticmodalitiessuchas immunotherapyandtargetedtherapy,newprogresshasbeenmadeinthe treatmentofcervicalcancer,whichhassignificantlyimprovedtheprognosisof patientswithcervicalcancer,especiallyincaseswheretraditional chemotherapy-therapyhasfailed.Whilethesetherapiesshowgreatpromise, theyarenotwithoutlimitationsandpotentialsideeffects,andfurtherresearch isstillneededtooptimizetheuseofthesetherapiesandidentifywhichpatients aremostlikelytobenefitfromthem
Ingeneral,theemergenceofinnovativetherapieshasbroughtnewhopeto cervicalcancerpatientsDuetothespacelimitation,onlyapartofcervical cancertreatmentmethodsareintroducedhereandnotalltherapiesarelisted. We'llalsobekeepinganeyeondevelopmentsincancerresearchand updatingreadersonthelatesttreatments.
Polyethyleneglycol(PEG)isoneofthemostwidelyusedlinkersintargeted therapiesAsaprofessionalmanufacturerofpharmaceuticalintermediates andPEGlinkers,HuatengPharmaisdedicatedtobeingyourmostreliable partnertoprovidehigh-qualityPEGlinkersforADCdrugs
References:
[1]Cervicalcancer，RetrievedFebruary27th,2023
fromhttps://www.who.int/news-room/fact-sheets/detail/cervical-cancer
[2]TargetedDrugTherapyforCervicalCancer，RetrievedFebruary27th,2023
fromhttps://www.cancer.org/cancer/cervical-cancer/treating/targeted-therapy. html
[3]ImmunotherapyforCervicalCancer，RetrievedFebruary27th,2023
fromhttps://www.cancer.org/cancer/cervical-cancer/treating/immunotherapy.h tml
Relatedarticles:
[1]TargetedDrugTherapyAndImmunotherapyForBreastCancer
[2].ApprovedAntibody–DrugConjugates(ADCs)andInClinicalTrials