1stInternationalSymposiumofMEXTProgram“FosteringHealthProfessionalsforChanging

NeedsofCancer”

GenomicMedicineKantoAcademicAllianceforFostering

CancerProfessionals

February17,Sat10:00�17:00ROSEHALL

(MaebashiChamberofCommerceandIndustry)

PROGRAM

Welcomeaddress

10:30�10:35 Prof.Yasuki ISHIZAKI(Dean,GunmaUniversityGraduateSchoolofMedicine)

SessionI.CancerGenomicMedicine

Moderator:HisahiroMATSUBARA(GraduateSchoolofMedicine,ChibaUniversity)

10:35~11:15

Implementationof“ClinicalSequencing”inCancerGenomeMedicineinJapan

Dr.TakashiKOHNO(DivisionofGenomeBiology,NationalCancerCenterResearchInstitute/DivisionofTranslationalResearch, ExploratoryOncologyResearch&ClinicalTrialCenter(EPOC),NationalCancerCenter,JPN)

11:15~11:50

GenomeSequencingAnalysisforCancerResearchandPrecisionMedicine

Dr.Hidewaki NAKAGAWA(LaboratoryforGenomeSequencingAnalysis,RIKENCenterforIntegrativeMedicalSciences,JPN)

11:50~12:50 Lunch

Session�.Toward Further Progress�OmicsAnalysisandBioinformaticsModerator:Prof.MasahikoNISHIYAMA

(GunmauniversityGraduateSchoolofMedicine)

12:50 ~13:30

IdentificationofNovelTherapeuticTargetsforCancerBasedontheOmicsCancer-Assciated Fibroblasts:TumorAlliesandFoes

Dr.AndreiTURTOI(TumorMicroenvironmentandResistancetoTreatment,InstituteofCancerResearchofMontpellier,FRA)

13:30 ~14:10

InnovativestrategiestoidentifyandvalidatenewOMICsbiomarkerswithhightranslationalpotentialfordiagnostic,prognosticandtreatmentinoncology

Prof.VincentCASTRONOVO(LaboratoryofMetastasesResearch,GIGA-CANCER,LiegeUniversity,BEL)

14:10 ~14:50

Thedynamiccerebrospinalfluidproteomeandaperspectiveonanewclassofbiomarkers

Prof.JacquesCOLINGE(CancerBioinformaticsandSystemBiology,,InstituteofCancerResearchof Montpellier,FRA)

14:50 ~15:00 Coffee Break

Guidance Session forStudents:MeettheExperts

15:00 ~16:55

Studentattendancewillbeseparatedinto5groupsandrotate5stationstodirectlyasksomethingto5invitedspeakersinordertobeaspecialistofCancerGenomicMedicine.Eachinvitedspeakerswillgiveadvicesandsupervisetostudentsfromaviewpointofeachspecialfield.

ClosingRemarks

16:55�17:00 Prof.Nobuhiro OHKOHCHI(ProjectDirector/GraduateSchoolofComprehensiveHuman

Science,UniversityofTsukuba)

TakashiKohno,Ph.D

Position:Chief, DivisionofGenomeBiology,ResearchInstitute

Chief, DivisionofTranslationalGenomics,ExploratoryOncology ResearchandClinicalTrialCenter(EPOC)NationalCancerCenter,Japan

Address:5-1-1,Tsukiji,Chuo-ku,Tokyo1040045,JapanTEL: +81-3-3547-5272E-mail: tkkohno@ncc.go.jpEDUCATION

KyotoUniversity,SchoolofPharmacy,Kyoto,Japan (1985-1989)KyotoUniversity,GraduateSchoolofPharmacy,Kyoto,Japan(1989-1991)TokyoUniversity,GraduateSchoolofMedicine,Tokyo,Japan(1991-1995)

WORKEXPERIENCE Researcher,BiologyDivision(Dr.YokotaLab)

NationalCancerCenterResearchInstitute(1995-2000)SectionHead,BiologyDivision(Dr.YokotaLab)NationalCancerCenterResearchInstitute(2000-2010)Chief, DivisionofGenomeBiology NationalCancerCenterResearchInstitute(2011-present)Chief, DivisionofTranslationalGenomicsEPOC,NationalCancerCenter(2013-present)

CERTIFICATION DoctorofPhilosophy,TokyoUniversity(1995)RESEARCHINTEREST

Cancergenomemedicine

Dr.TakashiKohnoiscurrentlyaChief inDivisionofGenomeBiologyofNationalCancerCenterResearchInstitute,Japan. Dr.KohnograduatedfromKyotoUniversityin1989.HereceivedPhDfromTokyoUniversity.From1995,hehasstudiedlungcancergeneticsandgenomicsinNationalCancerCenter.HisrepresentativeresearchproductisthefindingofRETfusioninlungadenocarcinoma anditstranslationtolungcancerclinic.HeisalsoaChiefofDivisionofTranslationalResearch,ExploratoryOncologyResearchandClinicalTrialCenter,NationalCancerCenterResearchInstitute.Hisresearchareaincludesgenomics,genetics(polymorphisms),andcancergenomemedicine.

Implementationof“ClinicalSequencing” inCancerGenome

Medicine inJapanTakashiKohnoDivisionofGenomeBiology,NationalCancerCenterResearchInstituteDivisionofTranslationalGenomics,ExploratoryOncologyResearchandClinicalTrialCenter,NationalCancerCenterIn oncology, actionable mutations (alterations) in cancer-associated genes arecritical in terms of the selection of therapeutic approaches. Next-generationsequencing(NGS)oftumorsampleDNA(i.e.,clinicalsequencing)canguideclinicalmanagement by providing diagnostic or prognostic data, and facilitating theidentification of potential treatment regimens, such as molecular-targeted andimmunecheckpointblockade therapies.IntheU.S.,avarietyofmulti-genepanelshavebeendevelopedandimplementedforthispurpose.InJapan,severalacademicinstitutionshavenowperformeddetailedinvestigationsofthefeasibilityandvalueofclinical sequencing,andcancersocietieshaveissuedconsensusclinicalpracticeguidelines forNGS-based tests.Theseeffortswill facilitate theimplementationofcancergenomemedicineinJapan. 1)KohnoTetal.KIF5B-RETfusionsinlungadenocarcinoma.NatMed,2012.2)YohKetal.VandetanibinpatientswithpreviouslytreatedRET-rearrangedadvancednon-small-celllungcancer(LURET):anopen-label,multicentrephase2trial.LancetRespirMed,2017.

3)Tanabeetal.Comprehensivescreeningoftargetmoleculesbynext-generationsequencinginpatientswithmalignantsolidtumors:guidingentryintophaseIclinicaltrials.MolCancer,2016.

3)KohnoT.Implementationof"ClinicalSequencing"incancergenomemedicinein�Japan.CancerSci,2018,inpress.

HidewakiNakagawa,MD,PhD

1991 OsakaUniversity,SchoolofMedicine (M.D.)

1991 OsakaUniversityHospital,GeneralSurgery,Resident

1992 OsakaUniversityHospital,ICU/Anesthesiology,Resident

1993 NationalOsakaHospital,GIsurgeryandbreastsurgey,Resident

1996 OsakaUniversity,GraduateSchoolofMedicine(Ph.D. 2000)

1999 TheOhioStateUniversity,HumanCancerGeneticsProgram,

Postdoctoralfellow

2003 AssitantProfessor/AssociateProfessor,HumanGenomeCenter,Instituteof

MedicalScience, TheUniversityofTokyo

2008 LaboratoryHead,LaboratoryforBiomarkerDevelopment,RIKENCenterfor

GenomicMedicine

2013- LaboratoryHead,LaboratoryforGenomeSequencing Analysis,RIKENCenter

forIntegrativeMedical Sciences

2015- ProgramOfficerofBiobank/GenomicMedicineprojectinAMED

Dr.HidewakiNakagawa graduated fromOsakaUniversitySchoolofMedicinein1991, and

hecompletedtraininginclinicaloncologyofGI&breastcancersandcriticalcaremedicine

asasurgeon.HeobtainedhisPhDin 2000fromOsakaUniversityforgenomic researchof

hereditarycoloncancer.Afterfouryearspostdoctoraltrainingofcoloncancergenomicsat

theHumanCancerGeneticsProgram,TheOhioStateUniversity,USA,hereturnedtoJapan

asanassistant/associateprofessoratInstituteofMedicalScience,TheUniversityofTokyo,

wherehewasdedicatedtotherapeutictargetscreeningforpancreaticandprostatecancers.

In2008, hemoved toRIKENasa team leader of genomic medicine. Hisrecentresearch

focuses on cancer genomics by whole genome sequencing and cancer biomarker

development using next-generation sequencing.He hasbeen workingforcancer genome

sequencing analysisof livercancerandGI cancersasoneof thePIsof ICGC/TCGA

project. His main interest is genome-based personalized medicine and cancer

patientcare.

GenomeSequencing Analysis forCancerResearchandPrecision

Medicine

HidewakiNakagawaRIKENCenterforIntegrativeMedicalSciencesCancerisessentiallya“diseaseofthegenome”whichdevelopsandevolveswiththeaccumulationofavarietyofmutationsinthebackgroundofgermlinevariants,andsome driver mutations such as EGFR, HER2, and BRCA1/2 were successfullytargetedfortreatment.Explosiveadvancesofnext-generationsequencer(NGS)andcomputational analyses handling massive data enable us to comprehensivelyanalyze cancergenome profiles in researchandclinical levels, suchas targetedsequencingforhundredsofgenes,wholeexomesequencing(WES),RNAsequencing(RNA-Seq),and eventually whole genome sequencing (WGS) or cell-free DNAsequencing.Theseapproachescombinedwith mathematicalanalysis andother -omics analysis canclarify theunderlyingcarcinogenesis andcancer immunologyandachievemolecular sub-classification of cancer,which facilitates discovery ofgenomicbiomarkersandpersonalizedcancermedicine.Ipresentrecenttechnicalapproaches for cancer genome sequencing and the future direction of cancergenomesequencing,anddiscussitsutilityandlimitationofananalysisplatformandmutationinterpretationforcancergenomicsandcancerprecisionmedicine.�

Dr.TurtoiAndreiTeamLeader“TumorMicroenvironment andResistance toTreatment”InstitutdeRechercheenCancérologie deMontpellier/InsermU1194,Montpellier,France

EDUCATION01.04.2008 PhD(FacultyofBiology/DepartmentofGenetics,TechnicalUniversity Dresden,Germany.)2004 Dipl.Ing.(FacultyofChemicalEngineering/ Universityof Applied Sciences, Aachen, Germany.)2003 B.Eng.(FacultyofChemical Engineering/ UniversityofApplied Sciences, Aachen, Germany.)1999 International Baccalaureate (IB)(UnitedWorld Colleges, Pune, India.)PREVIOUS POSITIONS07.2016– InvitedLecturer(AssistantProfessor)09.2016 DepartmentofMolecularPharmacologyandOncology, GraduateSchoolofMedicine, UniversityofGunma,Maebashi,Japan.2015–2016 FNRSScientificCollaborator (TelevieFellowship) FacultyofMedicine/GIGA-Cancer,MetastasisResearchLaboratory, UniversityofLiege,Liege, Belgium.05.2015– InvitedLecturer(AssistantProfessor)09.2015 DepartmentofMolecularPharmacologyandOncology, GraduateSchoolofMedicine, UniversityofGunma,Maebashi,Japan.2012–2015 FNRSChargedeRecherché FacultyofMedicine/GIGA-Cancer,MetastasisResearchLaboratory, UniversityofLiege,Liege, Belgium.2009–2012 PrincipalInvestigator FacultyofMedicine/GIGA-Cancer,MetastasisResearchLaboratory, UniversityofLiege,Liege, Belgium.2008–2009 PostDoctoralFellow FacultyofSciences/DepartmentofChemistry,MassSpectrometryLaboratory, UniversityofLiege,Liege, Belgium.2005–2008 PhDFellow InstituteofMedicine, LaboratoryofRadiationBiology,ForschungszentrumJülich, Germany.2003–2004 ResearchFellow DepartmentofMarineChemistry,AlfredWegener InstituteforPolarandMarine Research,Bremerhaven,Germany.

Cancer-AssciatedFibroblasts:TumorAllies andFoes

AndreiTurtoi

InstitutduCancerMontpellier,Montpellier34090,France;

INSERMU1194,Montpellier34090,France;

InstitutdeRechercheenCancérologiedeMontpellier,Montpellier34090,France;

UniversitéMontpellier,Montpellier34298,France;

Cancerassociatedfibroblastsarethemajorcomponentofthetumormicroenvironment

&a rich sourceofgrowth factors,pro-angiogenicmolecules andmatrix proteins.In

contrast to for examplemacrophages,CAFarealmost exclusively regardedas pro-

tumorigenicelementsandassuchtheyhavebeenproposedaseligibletumortargets.

Unfortunately,CAF-directedtargetedtherapieshavethusfarnotproducedthedesired

anti-tumor effects. These have either showed only modest tumor control or,

surprisingly,have inducedtumoralprogression.Emergingevidencesuggest thatour

simplistic pictureof CAF is notcorrect andthat thesecells mayalso have intrinsic

tumor-defensiveproperties.Futurestudiesof tumormicroenvironment andnotably

CAF will thus inevitably relay on single cell approaches,enabling a context and

spatially-dependentobservationof this highlyheterogeneouscell population. Inthe

presenttalk Iwill touchuponpastandpresentworkssupportingsuchdifferentiated

pictureofCAFaswellaspresentsomenewestresearchdatafromourlab.

VincenzoCASTRONOVOProfessorFacultyofMedicine,UniversityofLiège

Workaddress:UniversityofLiège-MetastasesResearchLaboratory TourdePathologie, +4,Bât.B23-B-4000Liège Tél.:+32(0)43662479-e-mail:vcastronovo@ulg.ac.beEducation

MedicalDoctor,Surgeryandobstetrics,UniversityofLiège,1983–SummaCumLaude.PhDinbiomedicalsciences,UniversityofLiège,1987–SummaCumLaude.Agrégédel’Enseignement Supérieur,UniversityofLiège, 1992–SummaCumLaude.Board-Certified in Obstetricsand Gynecology, Universityof Liège, 1993 – Summa CumLaude.

UniversitycareerHeadofMetastasesResearchLaboratory,UniversityofLiège(Since 1992).SupervisorofGynecologics-ObstetricalDepartment.UniversityofLiège(1993-1998).MaîtredeConférences. UniversityofLiège(1994-1998).FounderanddirectoroftheMetastasesResearchLaboratory(1992-todate)MaîtredeRecherches(FondsNationaldelaRechercheScientifique (1994-1998).MedicalDirectoroftheCentreAnti-Cancer.(1995-2003).DirectoroftheCenterofExperimental CancerResearch(CRCE). UniversityofLiège(2002-2007).Professor (Fulltime). FacultyofMedicine, UniversityofLiège(2005-2010).HeadofGIGA-Cancer.UniversityofLiège(2008-2011).FullProfessor(Biology).FacultyofMedicine, UniversityofLiège(Since2011).MemberoftheRoyalBelgianAcademyofMedicine.

Innovative strategies toidentify andvalidatenewOMICsbiomarkerswithhightranslationalpotential fordiagnostic,

prognostic andtreatment inoncology

VincentCastronovo1,AndreiTurtoi1,BrunellaCostanza1andMasahikoNishiyama2

MetastasisResearchLaboratory,GIGACancer,UniversityofLiège,Liège, Belgium DepartmentofMolecularPharmacologyandOncology,GunmaUniversityGraduateSchoolofMedicine,Maebashi, Gunma,Japan �Biomarker discovery is a crucial step for cancer early diagnosis, prognosis,predictionoftherapyresponseandspecificeffectivetargetedtherapies,particularlyin the field ofoncology. Thediscovery of biomarkers thatare readily accessiblethrough the circulating blood andare selectively overexpressed in pathologicaltissueshasbecomeamajorresearchobjective.Thisgroupofmoleculeshasahighpotentialto serveasatool forimagingandtargetedcancertherapyapproaches.Inthis therapeutic concept, specific cancer proteins are reachedby intravenouslyadministered ligands thatare coupled to cytotoxic drugs,able to inducecancerdestruction while sparing normal tissues. Current high-throughput proteomicanalysis allows for the identification of a high number of proteins that aredifferentiallyexpressedinthecanceroustissues.However,suchapproachesprovideno information regarding theaccessibility of thebiomarkers and,therefore,thepossibility for thesediscoveredproteinsto betargeted.Tobypass this limitation,whichclearlyslows thediscoveryofsuchbiomarkers,wehavedeveloped,appliedand validated innovative technologies to efficiently identify accessible antigensfromclinically relevant samples.Anotherchallenge in thebiomarker field is theidentification of diagnostic and prognostic biomarkers from early lesions,measurableinliquidbiopsies.Freshhumanmaterialofhighqualityisrequiredforbiomarkerdiscoverybutisoftennotavailablewhenitistotally requiredforclinicalpathology investigation. Hence,all OMICsstudies aredoneon residual andlessclinically relevantbiological samples.Wehavedevelopedaninnovative,simple,andnon-destructive, procedure named EXPEL that uses rapid, pressure-assisted,interstitial fluid extrusion, preserving the specimen for full routine clinicalpathology investigation. In themeantime, the techniqueallows acomprehensiveOMICsanalysis (proteins,metabolites,miRNAsandDNA).Asproofofconcept,wehave applied EXPEL on freshly collected human colorectal cancer and livermetastases tissues. We demonstrate that the procedure efficiently allows theextraction, within a few minutes, of a wide variety of biomolecules holdingdiagnostic andprognostic potential while keepingboth tissue morphology andantigenicityunaltered.Ourmethodenables,forthe first time,bothclinicians andscientiststoexploreidenticalclinicalmaterialregardlessofitsoriginandsize,whichhasamajorpositive impactontranslationtotheclinic.Ourtechnologyopensaneweraforbiomarkersdiscoveryandwillhaveamajorimpactontranslationalresearch.Wetrustthatthismethodmeetstheemergingconceptofprecisionmedicinewherecancerdiagnosisandtreatmentaretailoredtotheindividualpatientcharacteristics.

JacquesColinge, PhD, ProfessorIRCM,ICM,andFacultyofMedicineUniversityofMontpellierMontpellier,France

ResearchCareerPh.D. inMathematics,UniversityofGeneva,Switzerland1998-2000 Bioinformatician&ScientistI,SeronoPharmaceuticalResearchInstitute,Geneva2000-2005 HeadofMassSpectrometryBioinformaticsandParallelComputing, GeneProt

Inc.,Geneva2005-2006 ProfessorofBioinformatics,UpperAustriaUniversityofAppliedSciences2006-2014 HeadofBioinformatics,CeMM, Vienna,Austria2009- Habilitation&AdjunctProfessorinBioinformatics,TechnischeUniversitätGraz2014- FullProfessorUniversityofMontpellier&TeamLeaderatIRCM2014- AdjunctPI,CeMM,ViennaResearchInterests

Systemsandnetworkbiologymethoddevelopmentapplied tocancerand immunologyPersonalizedcancertherapyComputationalproteomics

Thedynamiccerebrospinal fluidproteomeandaperspective onanewclassofbiomarkers

JérômeVialaret1,ChristopheHirtz1,MaxenceOry2,GuillaumeGrasCombe3,LucBauchet3,MarineGirard1,AudreyGabelle1,4,SylvainLehmann1,JacquesColinge2,5

1CHRUdeMontpellier,UniversitédeMontpellierandINSERMU1183,IRMB,LaboratoiredeBiochimieProtéomiqueClinique,Montpellier,France2IRCM,InstitutdeRechercheenCancérologiedeMontpellier,INSERMU1194,Montpellier,France3ServicedeNeurochirurgie,CHRUdeMontpellier,hôpitalGuideChauliac,Montpellier,INSERMU1051andUniversitédeMontpellier,Montpellier,France4CentreMémoiredeRessourcesetdeRechercheLanguedoc-Roussillon,Département deNeurologie,CHRUdeMontpellier,hôpitalGuideChauliac,Montpellier,France5ICM,InstitutduCancerdeMontpellier,Montpellier,FranceIntravenous administration of stable isotope labeled amino acid (13C6-leucine) tohumansrecentlymade it possible to study themetabolism of specific biomarkers incerebrospinal fluid(CSF)using targetedmassspectrometry (MS).Wehaveappliedanunbiased, large-scale approach to obtain hundredsof leucine-containing peptides inparallel using high-resolution MS. Advanced signal processing and mathematicalmodeling techniquesallowed us to determinetherates of synthesisandclearanceofmore than200proteinsintheCSF.Large-scalemeasuresobtainedfromoneindividualhavebeenconfirmedbytargetedmeasuresforadozenofproteinsin4patients.Theseunpublishedresultspavethewayto thestudyofproteomedynamicstounravelnovel biomarkers witnessing metabolic differences, abnormal protein turnover orderegulatedfluxesbetweenbiologicalcompartments,e.g.CSFandblood,indiseases.Ourresultsdemonstratethatthisnewfieldofproteomic investigation canbeconductedinhumanpatientsandbiological fluidsbutthetechniqueisobviouslyapplicabletoanimalmodelsandsolidtissueswithadaptations.

MEXTProgram“FosteringHealthProfessionalsforChangingNeedsofCancer”

KantoAcademicAllianceforFosteringCancerProfessionals

GunmaUniversityGraduateSchoolofMedicine