Cancer metabolism: looking forward | Nature Reviews Cancer

Tumour initiation and progression requires the metabolic reprogramming of cancer cells. Cancer cells autonomously alter their flux through ... Skiptomaincontent Thankyouforvisitingnature.com.YouareusingabrowserversionwithlimitedsupportforCSS.Toobtain thebestexperience,werecommendyouuseamoreuptodatebrowser(orturnoffcompatibilitymodein InternetExplorer).Inthemeantime,toensurecontinuedsupport,wearedisplayingthesitewithoutstyles andJavaScript. Advertisement nature naturereviewscancer perspectives article Subjects CancermetabolismCancermicroenvironmentCancertherapy AbstractTumourinitiationandprogressionrequiresthemetabolicreprogrammingofcancercells.Cancercellsautonomouslyaltertheirfluxthroughvariousmetabolicpathwaysinordertomeettheincreasedbioenergeticandbiosyntheticdemandaswellasmitigateoxidativestressrequiredforcancercellproliferationandsurvival.Cancerdrivermutationscoupledwithenvironmentalnutrientavailabilitycontrolfluxthroughthesemetabolicpathways.Metabolites,whenaberrantlyaccumulated,canalsopromotetumorigenesis.Thedevelopmentandapplicationofnewtechnologiesoverthelastfewdecadeshasnotonlyrevealedtheheterogeneityandplasticityoftumoursbutalsoallowedustouncovernewmetabolicpathwaysinvolvedinsupportingtumourgrowth.Thetumourmicroenvironment(TME),whichcanbedepletedofcertainnutrients,forcescancercellstoadaptbyinducingnutrientscavengingmechanismstosustaincancercellproliferation.ThereisgrowingappreciationthatthemetabolismofcelltypesotherthancancercellswithintheTME,includingendothelialcells,fibroblastsandimmunecells,canmodulatetumourprogression.Becausemetastasesareamajorcauseofdeathofpatientswithcancer,effortsareunderwaytounderstandhowmetabolismisharnessedbymetastaticcells.Additionally,thereisanewinterestinexploitingcancergeneticanalysisforpatientstratificationand/ordietaryinterventionsincombinationwiththerapiesthattargetmetabolism.InthisPerspective,wehighlightthesemainthemesthatarecurrentlyunderinvestigationinthecontextofinvivotumourmetabolism,specificallyemphasizingquestionsthatremainunanswered. Thisisapreviewofsubscriptioncontent Accessoptions Accessthroughyourinstitution Changeinstitution Buyorsubscribe SubscribetoJournalGetfulljournalaccessfor1year55,14€only4,60€perissueSubscribeAllpricesareNETprices.VATwillbeaddedlaterinthecheckout.Taxcalculationwillbefinalisedduringcheckout.BuyarticleGettimelimitedorfullarticleaccessonReadCube.$32.00BuyAllpricesareNETprices. Additionalaccessoptions: Login Learnaboutinstitutionalsubscriptions Fig.1:Metabolicandsignallingpathwayssupportingtumourbiomassproduction.Fig.2:Signallingandnon-canonicalmechanismsincancermetabolism.Fig.3:BiologyofROSincancercells.Fig.4:MetaboliccrosstalkofcellswithintheTME.Fig.5:Metabolismregulatesmultistepsofmetastasis.Fig.6:Personalizedmedicineapproachtotargetingcancermetabolism. 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DownloadreferencesAcknowledgementsTheauthorsaregratefultoR.Deberardinis(UTSouthwestern)forhelpfulandinsightfulcomments.TheythankL.DieboldandC.ReczekfromtheChandellaboratoryfortheirhelpfulinputandediting.ThisworkwasfundedbyNationalInstitutesofHealth(NIH)Grant5R35CA197532.Wehavelargelyconfinedthereferencestothepastfewyearswiththeemphasisoninvivofindingsinthefieldandhavecitedmanyexcellentreferencesinthepastyear.AuthorinformationAffiliationsDepartmentofMedicine,NorthwesternUniversityFeinbergSchoolofMedicine,Chicago,IL,USAInmaculadaMartínez-Reyes & NavdeepS.ChandelDepartmentofBiochemistryandMolecularGenetics,NorthwesternUniversityFeinbergSchoolofMedicine,Chicago,IL,USANavdeepS.ChandelAuthorsInmaculadaMartínez-ReyesViewauthorpublicationsYoucanalsosearchforthisauthorin PubMed GoogleScholarNavdeepS.ChandelViewauthorpublicationsYoucanalsosearchforthisauthorin PubMed GoogleScholarContributionsTheauthorscontributedequallytoallaspectsofthearticle.CorrespondingauthorCorrespondenceto NavdeepS.Chandel.Ethicsdeclarations Competinginterests N.S.C.isonthescientificadvisoryboardofRafaelPharmaceuticalsandPenroseTherapeuTx.I.M.-R.declaresnocompetinginterests. AdditionalinformationPeerreviewinformationNatureReviewsCancerthanksC.Frezza,E.Whiteandtheother,anonymous,reviewer(s)fortheircontributiontothepeerreviewofthiswork.Publisher’snoteSpringerNatureremainsneutralwithregardtojurisdictionalclaimsinpublishedmapsandinstitutionalaffiliations.GlossaryAutophagy Ahighlyregulatedprocessthroughwhichproteinsandorganellesaredeliveredtothelysosomeanddegraded. Ferroptosis Adistinctformofprogrammedcelldeaththatrequiresreactiveoxygenspecies(ROS)andironaccumulationtocauselethallipidperoxidation. Hyaluronidase Anenzymethatdegradeshyaluronicacidintomonosaccharides. Peroxiredoxinenzymes Cysteine-dependentperoxidasesthatconverthydrogenperoxide(H2O2)towater. RightsandpermissionsReprintsandPermissionsAboutthisarticleCitethisarticleMartínez-Reyes,I.,Chandel,N.S.Cancermetabolism:lookingforward. 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