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

作者: Bruno Sainz , Nelson Dusetti , Juan Iovanna , Francisco Sánchez-Bueno , Manuel Hidalgo

DOI: 10.1016/J.CCELL.2019.03.002

关键词: Targeted therapyTumor progressionPancreatic cancerCancer researchc-RafKRASErlotinibPancreatic carcinomaMedicineComplete regression

摘要: 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 EGFR and c-RAF expression results in complete regression a significant percentage PDAC tumors driven by Kras/Trp53 mutations genetically engineered mice. Moreover, systemic elimination these targets induces toxicities are well tolerated. Response this targeted therapy correlates with transcriptional profiles resemble those observed human PDACs. Finally, inhibition effectively blocked tumor progression nine independent patient-derived xenografts carrying KRAS TP53 mutations. These open door development therapies patients.

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