Regorafenib Inhibits Growth, Angiogenesis, and Metastasis in a Highly Aggressive, Orthotopic Colon Cancer Model

摘要: The combination of target-specific drugs like bevacizumab with chemotherapeutics has improved treatment efficacy in advanced colorectal cancer (CRC). However, the clinical prognosis metastatic CRCs is still poor, and novel are currently assessed respect to their efficacies patients CRCs. In a phase III study, multikinase inhibitor regorafenib (BAY 73-4506) recently been shown prolong survival after standard therapies failed. present activity was investigated comparison angiogenesis DC101 highly aggressive, murine CT26 colon model. While for 10 days given at dose 34 mg/kg every third day significantly delayed tumor growth compared vehicle-treated animals, completely suppressed daily oral 30 mg/kg. Regorafenib also induced stronger reduction vascularization, as longitudinally vivo by dynamic contrast-enhanced MRI (DCE-MRI) confirmed immunohistochemistry. addition, inhibited angiogenic more strongly three times higher apoptosis rate than DC101. Even important, prevented formation liver metastases, whereas DC101-treated only reduced 33% vehicle group. amount infiltrating macrophages. These data show that exerts strong antiangiogenic, antitumorigenic, even antimetastatic effects on aggressive carcinomas indicative its high potential Mol Cancer Ther; 12(7); 1322–31. ©2013 AACR .