| Literature DB >> 30975481 |
María Teresa Blasco1, Carolina Navas1, Guillermo Martín-Serrano2, Osvaldo Graña-Castro2, Carmen G Lechuga1, Laura Martín-Díaz3, Magdolna Djurec3, Jing Li1, Lucia Morales-Cacho1, Laura Esteban-Burgos1, Javier Perales-Patón2, Emilie Bousquet-Mur3, Eva Castellano3, Harrys K C Jacob3, Lavinia Cabras3, Monica Musteanu1, Matthias Drosten1, Sagrario Ortega4, Francisca Mulero5, Bruno Sainz6, Nelson Dusetti7, Juan Iovanna7, Francisco Sánchez-Bueno8, Manuel Hidalgo9, Hossein Khiabanian10, Raul Rabadán10, Fátima Al-Shahrour2, Carmen Guerra11, Mariano Barbacid12.
Abstract
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.Entities:
Keywords: Cdk4; EGFR; Erlotinib; PDX tumor models; Pancreatic cancer; c-Raf; therapeutic mouse models; transcriptional profiles; tumor regression
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Year: 2019 PMID： 30975481 DOI： 10.1016/j.ccell.2019.03.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743