En direct

CRCM PhD Day 2021 will take place on May 28 2021 - Les mitochondries nouvelles cibles thérapeutiques potentielles dans le cancer du pancréas - La cycline A2, qui maintient l'homéostasie du côlon, est un facteur de pronostic dans le cancer colorectal -

04 2019 Cancer cell

Complete Regression of Advanced Pancreatic Ductal Adenocarcinomas upon Combined Inhibition of EGFR and C-RAF.

Auteurs

Blasco MT, Navas C, Martín-Serrano G, Graña-Castro O, Lechuga CG, Martín-Díaz L, Djurec M, Li J, Morales-Cacho L, Esteban-Burgos L, Perales-Patón J, Bousquet-Mur E, Jacob HKC, Cabras L, Musteanu M, Drosten M, Ortega S, Mulero F, Sainz B, Dusetti N, Iovanna J, Sánchez-Bueno F, Hidalgo M, Khiabanian H, Rabadán R, Al-Shahrour F, Guerra C, Barbacid M

Résumé

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.

Lire l‘article