Inhibition of TGF-β signalling in combination with nal-IRI plus 5-Fluorouracil/Leucovorin suppresses invasion and prolongs survival in pancreatic tumour mouse models.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies. TGF-β is strongly expressed in both the epithelial and stromal compartments of PDAC, and dysregulation of TGF-β signalling is a frequent molecular disturbance in PDAC progression and metastasis. In this study, we investigated whether blockade of TGF-β signalling synergizes with nal-IRI/5-FU/LV, a chemotherapy regimen for malignant pancreatic cancer, in an orthotopic pancreatic tumour mouse model. Compared to nal-IRI/5-FU/LV treatment, combining nal-IRI/5-FU/LV with vactosertib, a TGF-β signalling inhibitor, significantly improved long-term survival rates and effectively suppressed invasion to surrounding tissues. Through RNA-sequencing analysis, we identified that the combination treatment results in robust

SUBMITTER: Hong E 

PROVIDER: S-EPMC7031242 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature