Purpose: The mammalian target of rapamycin (mTOR) is frequently activated in epithelial ovarian cancer, and is regarded as an attractive therapeutic target for therapy. Preclinical investigations using rapamycin and its analogs have demonstrated significant growth-inhibitory effects on the growth of ovarian cancer, but those researches were focused only on mTOR Complex 1 (mTORC1), not on mTOR Complex 2 (mTORC2). We investigated the activity of mTORC2 and its role in epithelial ovarian cancer. Experimental design: Using human ovarian cancer samples and cell lines, (serous adenocarcinoma and clear cell carcinoma), we first examined the expression and activity of mTORC2. We next investigated the role of mTORC2 on the proliferation and invasiveness of overian cancer cells by knocking down the expression of rictor. Moreover, using 2 pairs of everolimus-sensitive parental and everolimus-resistant sublines, we examined whether mTORC2 is involved in the mechanism of acquired resistance to everolimus. Results: mTORC2 is frequently activated in human ovarian cancer, especially in clear cell carcinoma of the ovary. mTORC2 stimulated the proliferation and invasiveness of ovarian cancer cells in vitro. mTORC2 was hyperactivated in everolimus-resistant sublines compared to their parental cell lines. Inhibition of mTORC2 activity by siRNA sensitize the everolimus-resistant ovarian cancer cells to everolimus. Conclusion: mTORC2 is frequently activated in epithelial ovarian cancer, and is a promising therapeutic target.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2228. doi:1538-7445.AM2012-2228