Development of resistance to FAK inhibition in pancreatic cancer is linked to stromal depletion.

ABSTRACT:

Objective

We investigated how pancreatic cancer developed resistance to focal adhesion kinase (FAK) inhibition over time.

Design

Pancreatic ductal adenocarcinoma (PDAC) tumours from KPC mice (p48-CRE; LSL-KRas^G12D/wt; p53^flox/wt) treated with FAK inhibitor were analysed for the activation of a compensatory survival pathway in resistant tumours. We identified pathways involved in the regulation of signal transducer and activator of transcription 3 (STAT3) signalling on FAK inhibition by gene set enrichment analysis and verified these outcomes by RNA interference studies. We also tested combinatorial approaches targeting FAK and STAT3 in syngeneic transplantable mouse models of PDAC and KPC mice.

Results

In KPC mice, the expression levels of phosph

SUBMITTER: Jiang H 

PROVIDER: S-EPMC7167297 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature