title: IGF1R-directed targeted therapy enhances the cytotoxic effect of chemotherapy in endometrial cancer.
abstract: 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 anti-apoptotic 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.
authors: Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Connie
authors: C
authors: Bitelman
authors: Rive
authors: R
authors: Sarfstein
authors: Menahem
authors: M
authors: Sarig
authors: Zohar
authors: Z
authors: Attias-Geva
authors: Ami
authors: A
authors: Fishman
authors: Haim
authors: H
authors: Werner
authors: Ilan
authors: I
authors: Bruchim
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D016889:Endometrial Neoplasms / Q000188:drug therapy*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D058990:Molecular Targeted Therapy; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007334:Insulin-Like Growth Factor I; C569480:dalotuzumab; D017526:Receptor, IGF Type 1; D002945:Cisplatin