Abstract
Abstract The type 1 insulin-like growth factor receptor (IGF-1R) and its associated signaling system play a significant role in carcinogenesis and progression of gastrointestinal malignancies, and thus have provoked great interest as a promising target for cancer treatment. The aim of our study was to assess the effects of a novel IGF-1R inhibitor, NVP-AEW541, on the cell proliferation and signal transduction of esophageal squamous cell carcinoma. Five human esophageal squamous carcinoma cell lines (TE-1, TE-4, TE-8, TE-10 and T.Tn) were treated with this inhibitor and the IC50 of NVP-AEW541 for each cell line was more than 1μM, exhibiting that these cells were less sensitive to this compound. The activation of IGF-1R and AKT were dose dependently blocked by NVP-AEW541. However, the activities of the key molecules in Ras-MAPK pathway was not significantly inhibited by NVP-AEW541 without any major mutation of Ras. These results indicate that esophageal squamous cell carcinoma may be resistant to targeting IGF-IR due to its maintenance of Ras-MAPK signaling. Thus, to explore the potential mechanism of resistance will contribute to the therapeutic application for NVP-AEW541. Citation Format: Munenori Takaoka, XiaoHong Bao, Huifang Hao, Naomasa Ishida, Takuya Fukazawa, Tomoki Yamatsuji, Minoru Haisa, Yoshio Naomoto. Esophageal cancer exhibits a resistance to the chemical inhibition of IGF-1R with a maintained Ras-MAPK activity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2694. doi:10.1158/1538-7445.AM2015-2694
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