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oai:repisalud.isciii.es:20.500.12105/147722024-11-29T14:46:43Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Blasco, María Teresa author Navas, Carolina author Martín-Serrano, Guillermo author Martín-Díaz, Laura author Li, Jing author Morales-Cacho, Lucia author Esteban-Burgos, Laura author Perales-Patón, Javier author Bousquet-Mur, Emilie author Castellano, Eva author Jacob, Harrys K C author Cabras, Lavinia author Sainz, Bruno author Dusetti, Nelson author Iovanna, Juan author Sánchez-Bueno, Francisco author Hidalgo, Manuel author Khiabanian, Hossein author Rabadán, Raul author Graña Castro, Osvaldo author Lechuga C, Lechuga CG author Djurec M, Djurec M author Musteanu, Mónica author Drosten, Matthias author Ortega Jimenez, Sagrario author Mulero, Francisca author Guerra, Carmen author Barbacid, Mariano author Al-Shahrour, Fatima author 2019-04-15 Five-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. Cancer Cell . 2019;35(4):573-587.e6. 10.1016/j.ccell.2019.03.002 1878-3686 Cancer cell 30975481 http://hdl.handle.net/20.500.12105/14772 Complete Regression of Advanced Pancreatic Ductal Adenocarcinomas upon Combined Inhibition of EGFR and C-RAF.