Combination therapy with mTOR and PI3 kinase inhibitors is broadly synergistic in a wide variety of endometrial cancer cells

[摘要] 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

[学科分类] 妇产科学

[关键词] PI3K;Akt;mammalian target of rapamycin;temsirolimus;BEZ235;endometrial cancer