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

ABSTRACT:

Purpose

KRAS is mutated in the majority of pancreatic ductal adenocarcinoma. MAPK and PI3K-AKT are primary KRAS effector pathways, but combined MAPK and PI3K inhibition has not been demonstrated to be clinically effective to date. We explore the resistance mechanisms uniquely employed by malignant cells.

Experimental design

We evaluated the expression and activation of receptor tyrosine kinases in response to combined MEK and AKT inhibition in KPC mice and pancreatic ductal organoids. In addition, we sought to determine the therapeutic efficacy of targeting resistance pathways induced by MEK and AKT inhibition in order to identify malignant-specific vulnerabilities.

Results

Combined MEK and AKT inhibition modestly extended the survival of KPC mice and increased

SUBMITTER: Ponz-Sarvise M 

PROVIDER: S-EPMC6858952 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature