IGF1R-directed targeted therapy enhances the cytotoxic effect of chemotherapy in endometrial cancer

This study evaluated the potential ability of MK-0646 to inhibit IGF1-mediated biological actions and cell signaling events in Type 1 and Type 2 endometrial cancer. We found that MK-0646 treatment significantly decreased IGF1R expression. In addition, pretreatment with MK-0646 decreased the IGF1-induced phosphorylation of IGF1R, AKT and ERK. Apoptosis analyses showed that MK-0646 abolished the antiapoptotic effect of IGF1. Furthermore, MK-0646 treatment abolished the IGF1-stimulatory effect on proliferation and enhanced the cytotoxic effect of cisplatin. These findings indicate that specific inhibition of IGF1R could be a useful therapeutic approach for Type 1 and Type 2 endometrial cancer. (c) 2013 Elsevier Ireland Ltd. All rights reserved.