Activation of
receptor tyrosine kinases is recognized as a hallmark of
cancer.
Vascular endothelial growth factor (
VEGF) and its receptor VEGFR are the prominent players in the induction of
tumor neoangiogenesis. Strategies to inhibit
VEGF and VEGFR are under intensive investigation in preclinical and clinical settings.
Regorafenib is a multikinase inhibitor targeting some VEGFR and other receptor
kinases. Preclinical results led to the FDA approval of
regorafenib for treatment of metastatic
colorectal cancer patients. Effects of this drug in pancreatic ductal
adenocarcinoma (PDAC) have not been investigated yet. Gene expression was assessed with real-time PCR analysis. In vitro cell viability, proliferation, apoptosis,
necrosis, migration, and invasion of the PDAC cells were assessed after
regorafenib treatment. Ex vivo anti-
tumor effects of
regorafenib were investigated in a spheroid model of PDAC. In vivo anti-
tumor effects of the drug were evaluated in a fertilized chicken egg model. In this work, we have demonstrated only a marginal anticancer effect of
regorafenib in PDAC in vitro and ex vivo. However, in the egg model of PDAC, this drug reduced
tumor volume. Besides,
regorafenib is capable of modulating the expression of cancer stem cell (CSC) markers and epithelial-to-mesenchymal transition (EMT) markers on PDAC cells. We found out that effects of
regorafenib on the expression of CSC and EMT markers are very heterogeneous and depend obviously on original expression of these markers. We concluded that
regorafenib might be a potential drug for PDAC and it should be investigated in future clinical trials.