Combining targeted therapy and immune checkpoint inhibitors in the treatment of metastatic melanoma

(整期优先)网络出版时间:2014-04-14
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Melanomaisthedeadliestformofskincancerandhasanincidencethatisrisingfasterthananyothersolidtumor.Metastaticmelanomatreatmenthasconsiderablyprogressedinthepastfiveyearswiththeintroductionoftargetedtherapy(BRAFandMEKinhibitors)andimmunecheckpointblockade(anti-CTLA4,anti-PD-1,andanti-PD-L1).However,eachtreatmentmodalityhaslimitations.Treatmentwithtargetedtherapyhasbeenassociatedwithahighresponserate,butwithshort-termresponses.Conversely,treatmentwithimmunecheckpointblockadehasalowerresponserate,butwithlongtermresponses.Targetedtherapyaffectsantitumorimmunity,andsynergymayexistwhentargetedtherapyiscombinedwithimmunotherapy.Thisarticlepresentsabriefreviewoftherationaleandevidenceforthepotentialsynergybetweentargetedtherapyandimmunecheckpointblockade.Challengesanddirectionsforfuturestudiesarealsoproposed.