Targeting Glucose Metabolism Sensitizes Pancreatic Cancer to MEK Inhibition.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is almost universally lethal. A critical unmet need exists to explore essential susceptibilities in PDAC and to identify druggable targets to improve PDAC treatment. KRAS mutations dominate the genetic landscape of PDAC and lead to activation of multiple downstream pathways and cellular processes. Here, we investigated the requirement of these pathways for tumor maintenance using an inducible Kras^G12D -driven PDAC mouse model (iKras model), identifying that RAF-MEK-MAPK signaling is the major effector for oncogenic KRAS-mediated tumor maintenance. However, consistent with previous studies, MEK inhibition had minimal therapeutic effect as a single agent for PDAC in vitro and in vivo. Although MEK inhibition partially do

SUBMITTER: Yan L 

PROVIDER: S-EPMC8338909 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature