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

  • Cancer Lett. 2013 Jul 10;335(1):153-9. doi: 10.1016/j.canlet.2013.02.009.
Connie Bitelman  1 ,  Rive Sarfstein ,  Menahem Sarig ,  Zohar Attias-Geva ,  Ami Fishman ,  Haim Werner ,  Ilan Bruchim
Affiliations
  • 1. Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
PMID: 23402816 DOI: 10.1016/j.canlet.2013.02.009
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.

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