arestillunclear forcancerpreventionandtherapy isundoubtedthatthisemergingscenariowillhaveimportant participation. Press prevention models IRPATHWAYASACANDIDATETARGETFORCANCER ANDTHERAPY VALIDATIONOFIRASATHERAPEUTICALTARGETINPRECLINICAL: in vivo and in vitro A largebodyofevidenceshavedemonstratedtheimportanceof IR rats expressionandchronichyperinsulinemiaincelltransforma andtumordevelopment. StudiesconductedinobeseZucker tion, resistantpatients aswellasininsulin Checkpoint the haveshownthatinsulinresistanceand hyperinsulinemiamaycauseabnormal stimulationofmitogenic tion intracellularsignalingandincreasedcellproliferationandmigra inspiteofselectiveattenuationofthePI3Kpathwayand andcancerwasamodelofchemicallyinducedcolontumor impairedglucosehomeostasis.Thefirstanimalmodellinking insulin in rats r The wheretheinjectionofinsulinenhancedtumorigenesis whereascalorierestrictionandlowfatdietexertedaprotective. Inadifferentmodelofratbreastcancerogenesis, theinduction of formationorcausedarapidregressionofestablishedtumors insulinopenicdiabetescompletelypreventedmammarytumor. Recentstudiescarriedoutintransgenictype2diabeticmice haveconfirmedandextendedthesefindings. InMKR miceseverehyperinsulinemiaaffectedbreastcancerprogression