Regorafenib (BAY 73‐4506): Antitumor and antimetastatic activities in preclinical models of colorectal cancer

摘要: Regorafenib, a novel multikinase inhibitor, has recently demonstrated overall survival benefits in metastatic colorectal cancer (CRC) patients. Our study aimed to gain further insight into the molecular mechanisms of regorafenib and assess its potential combination therapy. Regorafenib was tested alone with irinotecan patient-derived (PD) CRC models murine liver metastasis model. Mechanism action investigated using vitro functional assays, immunohistochemistry correlation CRC-related oncogenes. significant inhibition growth-factor-mediated vascular endothelial growth factor receptor (VEGFR) 2 VEGFR3 autophosphorylation, intracellular signaling human umbilical cells (HuVECs) lymphatic (LECs), also blocked migration LECs. Furthermore, inhibited proliferation 19 25 cell lines markedly slowed tumor five seven PD xenograft models. Combination significantly delayed after extended treatment four Reduced CD31 staining indicates that antiangiogenic effects contribute antitumor activity. Finally, disease progression model by inhibiting established metastases preventing formation new other organs. In addition, our results suggest displays antimetastatic activity, which may efficacy patients CRC. an increased effect could provide future option for