Ontology highlight
ABSTRACT: Significance
Compensatory upregulation of IGF1R and ERK-MAPK signaling limits the efficacy of autophagy inhibitors chloroquine and hydroxychloroquine, and their concurrent inhibition synergistically increases autophagy dependence and chloroquine sensitivity in pancreatic ductal adenocarcinoma.
SUBMITTER: Stalnecker CA
PROVIDER: S-EPMC8886214 | biostudies-literature | 2022 Feb
REPOSITORIES: biostudies-literature
Stalnecker Clint A CA Grover Kajal R KR Edwards A Cole AC Coleman Michael F MF Yang Runying R DeLiberty Jonathan M JM Papke Björn B Goodwin Craig M CM Pierobon Mariaelena M Petricoin Emanuel F EF Gautam Prson P Wennerberg Krister K Cox Adrienne D AD Der Channing J CJ Hursting Stephen D SD Bryant Kirsten L KL
Cancer research 20220201 4
The aggressive nature of pancreatic ductal adenocarcinoma (PDAC) mandates the development of improved therapies. As KRAS mutations are found in 95% of PDAC and are critical for tumor maintenance, one promising strategy involves exploiting KRAS-dependent metabolic perturbations. The macrometabolic process of autophagy is upregulated in KRAS-mutant PDAC, and PDAC growth is reliant on autophagy. However, inhibition of autophagy as monotherapy using the lysosomal inhibitor hydroxychloroquine (HCQ) h ...[more]