Identification of Resistance Pathways Specific to Malignancy Using Organoid Models of Pancreatic Cancer

Abstract

Analyses of normal and tumor pancreatic organoids revealed the importance of ERBB activation during MEK and AKT blockade primarily in the malignant cultures. The lack of ERBB hyperactivation in normal organoids suggests a larger therapeutic index. In our models, pan-ERBB inhibition was synergistic with dual inhibition of MEK and AKT, and the combination of a pan-ERBB inhibitor with MEK antagonists showed the highest activity both <i>in vitro</i> and <i>in vivo</i>.