Dysregulation of mammalian target of rapamycin (mTOR) signaling has been found in many human tumors, including endometrial cancer, and mTOR inhibitors have been utilized in clinical trials as targeted therapies with only limited success. Herein we identify a viable treatment alternative that overcomes temsirolimus-induced AKT phosphorylation in endometrial cancer. Our data suggest temsirolimus and BEZ235 inhibit different components of the AKT/mTOR signaling pathway to accomplish synergistic pathway inhibition, which is necessary for therapeutic efficacy to abrogate the increased signaling through AKT that occurs with mTOR inhibition alone
PI3K, Akt, mammalian target of rapamycin, temsirolimus, BEZ235, endometrial cancer
Copyright © Shujie Yang, Xue Xiao, Xiangbinb Meng, and Kimberly K. Leslie, 2011.
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Yang S, Xiao X, Meng X, Leslie KK. Combination therapy with mTOR and PI3 kinase inhibitors is broadly synergistic in a wide variety of endometrial cancer cells. Proc Obstet Gynecol. 2011 Jul 28;2(1):Article 6 [2 p.]. https://doi.org/10.17077/2154-4751.1103. Free full text article.