Targeted mTOR in Human Gynecologic Cancers

Yi-Jen Chen

《Journal of Cancer Molecules》 3卷4期 (2007/08) Pp. 101-106

https://doi.org/10.29685/JCM.200708.0001

並列摘要

The protein mammalian Target of Rapamycin (mTOR) is a conserved Serine/Threonine kinase that regulates cell growth and metabolism in response to environmental cues. When growth conditions are favorable, TOR is active and cells maintain a robust rate of ribosome biogenesis, translation initiation, and nutrient import. Aberrant high activity of mTOR complexes appears to be an underlying cause of human gynecologic cancers. In patients with advanced or recurrent gynecologic cancer survival is greatly diminished. At this time the focus of future research should be on the use of novel targeted agents. mTOR inhibition represents a promising treatment strategy for endometrial and breast cancer. The tumor growth-inhibitory properties of rapamycin were recognized early, although it was initially clinically developed for its immunosuppressive properties. Because rapamycin has an undesirable pharmaceutical profile, including poor water-solubility, some analogues of rapamycin, such as CCI-799 (tensirolimus), RAD001 (everolimus) and AP23573 (ARIAD), have been developed with improved pharmaceutical properties. mTOR inhibition by theses agents has shown remarkable anti-tumor activity against human gynecologic malignancies in vitro and in vivo, and these drugs are currently under evaluation in Phase I-II clinical trials. Moreover, mTOR inhibitors enhances chemosensitivity of paclitaxel and cisplatin in ovarian and cervical cancer cells. mTOR inhibitors may have a major role for the management of malignancies characterized by increased activity of the mTOR pathway. mTOR is an exciting target, and future research will determine the optimal use of agents directed at this pathway.

並列關鍵字

mTOR ； rapamycin ； target therapy ； mTORC1 ； endometrial cancer