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1、Chapter13ChemotherapeuticAgentsinCancerTreatmentandTryptophanMetabolismS.AltugKesikliandNiluferGulerAbstractCanceristheuncontrolleddivisionandaccumulationofcellsinanypartofthebody.Surgery,radiotherapy,andsystemictherapiesarethemaintreatmentstrategiesagains
2、tcancers.However,systemicchemotherapyhasvarioussideeffects,includingnausea,vomiting,myelosuppression,cardiotoxicity(withanthra-cyclines),neurotoxicity(withmitoticspindlepoisons),andnephrotoxicity(withplatinumanalogs).Althoughsurgerycanbecurativeinsomecases
3、,themainpur-posesofcancertreatments,especiallyinmetastaticcancerpatients,arethepallia-tionofsymptomsandincreasingsurvivalwithbetterqualityoflife.IncreasingtheefÞcacyanddecreasingthetoxicityofchemotherapeuticagentsarecurrentlythemainchallengesincancertreatm
4、ent,forwhichsubstantialefforthasbeengivenforyears.Melatoninisahormoneproducedinthepinealglandfromtheessentialaminoacidtryptophan.ItisoneofthestrongestantioxidantsidentiÞed,withadditionalchemopreventive,oncostatic,andtumorinhibitoryeffectsinavarietyofinvitr
5、oandinvivoexperimentalcancermodels.Inadditiontomelatoninsynthesis,tryptophanisinvolvedinnumerousmetabolicactivitiesinthehumanbody,includingthebio-synthesisofserotonin,kynurenine,andnicotinamide,therebyregulatingcircadianrhythm,learning,memory,sleep,behavio
6、r,mood,appetite,aging,growth,repro-duction,immunesystem,andcancerdevelopment.Therefore,tryptophan-relatedmetabolicpathwaysandcataboliteshavegainedconsiderableattention,especiallyinimprovingcancertreatmentandpredictingdiseaseactivityaswellaspatientsurvival.
7、Thischaptermainlyfocusesontherelationshipbetweentryptophanmetabolismandchemotherapy;theprognosticvalueoftryptophancatabolitesascancerbiomarkers,tryptophanmetabolism,andcancer-relatedfatigue;theassocia-tionbetweenmelatoninandcancertherapyaswellaschemotherap
8、ysideeffects;S.A.Kesikli,M.D.,Ph.D.DepartmentofBasicOncology,HacettepeUniversityCancerInstitute,06100Altindag,Ankara,Turkeye-mail:akesikli@gmail.comN.Guler,M.D.(*)ProfessorEmeritus,DepartmentofMedicalOncology
