Blasco, María TeresaNavas, CarolinaMartín-Serrano, GuillermoMartín-Díaz, LauraLi, JingMorales-Cacho, LuciaEsteban-Burgos, LauraPerales-Patón, JavierBousquet-Mur, EmilieCastellano, EvaJacob, Harrys K CCabras, LaviniaSainz, BrunoDusetti, NelsonIovanna, JuanSánchez-Bueno, FranciscoHidalgo, ManuelKhiabanian, HosseinRabadán, RaulGraña Castro, OsvaldoLechuga C, Lechuga CGDjurec M, Djurec MMusteanu, MónicaDrosten, MatthiasOrtega Jimenez, SagrarioMulero, FranciscaGuerra, CarmenBarbacid, MarianoAl-Shahrour, Fatima2022-07-272022-07-272019-04-15Cancer Cell . 2019;35(4):573-587.e6.http://hdl.handle.net/20.500.12105/14772Five-year survival for pancreatic ductal adenocarcinoma (PDAC) patients remains below 7% due to the lack of effective treatments. Here, we report that combined ablation of EGFR and c-RAF expression results in complete regression of a significant percentage of PDAC tumors driven by Kras/Trp53 mutations in genetically engineered mice. Moreover, systemic elimination of these targets induces toxicities that are well tolerated. Response to this targeted therapy correlates with transcriptional profiles that resemble those observed in human PDACs. Finally, inhibition of EGFR and c-RAF expression effectively blocked tumor progression in nine independent patient-derived xenografts carrying KRAS and TP53 mutations. These results open the door to the development of targeted therapies for PDAC patients.engVoRAnimalsApoptosisCarcinoma, Pancreatic DuctalCell Line, TumorCell ProliferationErbB ReceptorsErlotinib HydrochlorideGefitinibGene Expression Regulation, NeoplasticHumansMice, 129 StrainMice, Inbred C57BLMice, TransgenicMutationPancreatic NeoplasmsProtein Kinase InhibitorsProto-Oncogene Proteins c-rafProto-Oncogene Proteins p21(ras)Signal TransductionTumor BurdenTumor Suppressor Protein p53Xenograft Model Antitumor AssaysAtribución-NoComercial-CompartirIgual 4.0 Internacional30975481354573-587.e610.1016/j.ccell.2019.03.0021878-3686Cancer cellopen access