简介:Sincetheapprovalofrituximabin1997,monoclonalantibodies(mAbs)havebecomeanincreasinglyimportantcomponentoftherapeuticregimensinoncology.ThesuccessofmAbsasatherapeuticclassisaresultofgreatstridesthathavebeenmadeinmolecularbiologyandinbiotechnologyoverthepastseveraldecades.Currently,thereare14approvedmAbproductsforoncologyindications,andtherearetenadditionalmAbsinlatestagesofclinicaltrials.Comparedtotraditionalchemotherapeuticagents,mAbshaveseveraladvantages,includingalongcirculatinghalf-lifeandhightargetspecificity.Antibodiescanserveascytotoxicagentswhenadministeredalone,exertingapharmacologiceffectthroughseveralmechanismsinvolvingtheantigenbinding(Fab)and/orFcdomainsofthemolecule,andmAbsmayalsobeutilizedasdrugcarriers,targetingatoxicpayloadtocancercells.TheextremelyhighaffinityofmAbsfortheirtargets,whichisdesirablewithrespecttopharmacodynamics(i.e.,contributingtothehightherapeuticselectivityofmAb),oftenleadstocomplex,non-linear,target-mediatedpharmacokinetics.Inthisreport,wesummarizethepharmacokineticandpharmacodynamicsofmAbsthathavebeenapprovedandofmAbsthatarenearingapprovalforoncologyindications,withparticularfocusonthemolecularandcellularmechanismsresponsiblefortheirdispositionandefficacy.
简介:Radiationtherapyperformsanimportantfunctionincancertreatment.However,resistanceoftumorcellstoradiationtherapystillremainsaseriousconcern,sothestudyofradiosensitizershasemergedasapersistenthotspotinradiationoncology.Alongwiththerapidadvancementofnanotechnologyinrecentyears,thepotentialvalueofnanoparticlesasnovelradiosensitizershasbeendiscovered.Thisreviewsummarizesthelatestexperimentalfindingsbothinvitroandinvivoandattemptstohighlighttheunderlyingmechanismsofresponseinnanoparticleradiosensitization.
简介:Melanomaisthedeadliestformofskincancerandhasanincidencethatisrisingfasterthananyothersolidtumor.Metastaticmelanomatreatmenthasconsiderablyprogressedinthepastfiveyearswiththeintroductionoftargetedtherapy(BRAFandMEKinhibitors)andimmunecheckpointblockade(anti-CTLA4,anti-PD-1,andanti-PD-L1).However,eachtreatmentmodalityhaslimitations.Treatmentwithtargetedtherapyhasbeenassociatedwithahighresponserate,butwithshort-termresponses.Conversely,treatmentwithimmunecheckpointblockadehasalowerresponserate,butwithlongtermresponses.Targetedtherapyaffectsantitumorimmunity,andsynergymayexistwhentargetedtherapyiscombinedwithimmunotherapy.Thisarticlepresentsabriefreviewoftherationaleandevidenceforthepotentialsynergybetweentargetedtherapyandimmunecheckpointblockade.Challengesanddirectionsforfuturestudiesarealsoproposed.
简介:Lungcanceristhemostfrequentlydiagnosedcancerandaleadingcauseofcancermortalityworldwide,withadenocarcinomabeingthemostcommonhistologicalsubtype.Deeperunderstandingofthepathobiologyofnon-smallcelllungcancer(NSCLC)hasledtothedevelopmentofsmallmoleculesthattargetgeneticmutationsknowntoplaycriticalrolesinprogressiontometastaticdiseaseandtoinfluenceresponsetotargetedtherapies.Theprinciplegoalofprecisionmedicineistodefinethosepatientpopulationsmostlikelytorespondtotargetedtherapies.However,thecancergenomelandscapeiscomposedofrelativelyfew"mountains"[representingthemostcommonlymutatedgeneslikeKRAS,epidermalgrowthfactor(EGFR),andanaplasticlymphomakinase(ALK)]andavastnumberof"hills"(representinglowfrequencybutpotentiallyactionablemutations).Low-frequencylesionsthataffectadruggablegeneproductallowarelativelysmallpopulationofcancerpatientsfortargetedtherapytobeselected.