BoronNeutron Capture Therapy (BNCT) is a selective anti tumoralradiotherapybasedonanuclearreactionthatoccurswhen 10Batomsareirradiatedbylow-energythermalneutrons, leadingto celldeaththanks totheproductionofhigh-energyalpha-particles. Recent improvements of neutron facilities,mainly inJapan,will surelypermitanincreaseinBNCTcancertherapy.Ofnote, in2020 BNCTtreatmentofheadandneckcancerwasapproved, andnew clinical trialsstarted,also.Ofnote,althoughtheextensiveapplica tions ofmolecular investigations to investigate awide range of diseasesandtreatments, fewmolecular studieswereperformedon BNCT(Imamichietal.,Biology2023;Pericoetal.Cells2023)and onlyone(Ferrarietal.Molecules2019)concerningtheeffectBPA and BSHadministration on human. In this context, a synergic international cooperationhas beenestablished for biomarker dis coveryonefficacyandsafetyofBNCT;specifically,theclinicaltrials plannedatNationalCancerCenter (NCC)Hospital inJapan,based on¹⁰B-BPAadministrationandneutronirradiationofmelanomaand angiosarcomaof theskin,areinvestigatedbyintegratedgenomics, metabolomicsandproteomics(iGMP),performedatNCC,Councilof NationalResearch,GianninaGaslini InstituteinItalyandNagasaki University, toobtainthemolecularprofilesbeforeandafterBNCT. For iGMPinvestigation,biofluidsfrompatients(plasmaandurine), whicharenon-invasivesamples, isolatingtheextracellularvesicles (EVs) for proteomics analysis, mainly have been available. In addition, FFPE tissues of melanoma and angiosarcoma became available.RNA, proteinandmetaboliterawdataareprocessedto obtainprofiles, stratificationbycluster analysis anddifferentially expressed.Thedifferentomicsprofiles(thousandsofmolecules for eachsample)aresharedandcomparedusingcomputational tools, specifically by the systems biology approach, focused on the characterizationofmodifiedpathwaysrelatedtodiseaseandrecov eredduetothetherapy.Theseactivitieswillidentifybiomarkersand deregulatedpathwaysrelatedtotheeffectsofBoron10andneutron irradiationdosesusefultoimproveBNCTapplications,anddatawill be important for characterizingbiomarkers useful formonitoring efficacy and side effects of accelerator-based neutron capture therapy.
INTEGRATED MOLECULAR PROFILES TO INVESTIGATE EFFICACY AND SAFETY OF BORON NEUTRON CAPTURE THERAPY (BNCT)
Mauri, Pierluigi;Perico, Davide;Palma, Antonella De;Silvestre, Dario Di;
2024
Abstract
BoronNeutron Capture Therapy (BNCT) is a selective anti tumoralradiotherapybasedonanuclearreactionthatoccurswhen 10Batomsareirradiatedbylow-energythermalneutrons, leadingto celldeaththanks totheproductionofhigh-energyalpha-particles. Recent improvements of neutron facilities,mainly inJapan,will surelypermitanincreaseinBNCTcancertherapy.Ofnote, in2020 BNCTtreatmentofheadandneckcancerwasapproved, andnew clinical trialsstarted,also.Ofnote,althoughtheextensiveapplica tions ofmolecular investigations to investigate awide range of diseasesandtreatments, fewmolecular studieswereperformedon BNCT(Imamichietal.,Biology2023;Pericoetal.Cells2023)and onlyone(Ferrarietal.Molecules2019)concerningtheeffectBPA and BSHadministration on human. In this context, a synergic international cooperationhas beenestablished for biomarker dis coveryonefficacyandsafetyofBNCT;specifically,theclinicaltrials plannedatNationalCancerCenter (NCC)Hospital inJapan,based on¹⁰B-BPAadministrationandneutronirradiationofmelanomaand angiosarcomaof theskin,areinvestigatedbyintegratedgenomics, metabolomicsandproteomics(iGMP),performedatNCC,Councilof NationalResearch,GianninaGaslini InstituteinItalyandNagasaki University, toobtainthemolecularprofilesbeforeandafterBNCT. For iGMPinvestigation,biofluidsfrompatients(plasmaandurine), whicharenon-invasivesamples, isolatingtheextracellularvesicles (EVs) for proteomics analysis, mainly have been available. In addition, FFPE tissues of melanoma and angiosarcoma became available.RNA, proteinandmetaboliterawdataareprocessedto obtainprofiles, stratificationbycluster analysis anddifferentially expressed.Thedifferentomicsprofiles(thousandsofmolecules for eachsample)aresharedandcomparedusingcomputational tools, specifically by the systems biology approach, focused on the characterizationofmodifiedpathwaysrelatedtodiseaseandrecov eredduetothetherapy.Theseactivitieswillidentifybiomarkersand deregulatedpathwaysrelatedtotheeffectsofBoron10andneutron irradiationdosesusefultoimproveBNCTapplications,anddatawill be important for characterizingbiomarkers useful formonitoring efficacy and side effects of accelerator-based neutron capture therapy.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
