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Figlin RA , Brown E , Armstrong AJ , Akerley W , Benson AB 3rd , Burstein HJ , Ettinger DS , Febbo PG , Fury MG , Hudes GR , Kies MS , Kwak EL , Morgan RJ Jr , Mortimer J , Reckamp K , Venook AP , Worden F , Yen Y
NCCN Task Force Report: mTOR inhibition in solid tumors
J Natl Compr Canc Netw. 2008 Sep;6 Suppl 5 :S1-S20; quiz S21-S22
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The mammalian target of rapamycin (mTOR) protein complex functions as an integration center for various intracellular signaling pathways involving cell cycle progression, proliferation, and angiogenesis. These pathways are frequently dysregulated in cancer, and therefore mTOR inhibition is a potentially important antitumor target. Commercially available mTOR inhibitors include rapamycin (i.e., sirolimus) and temsirolimus. Other agents under investigation include everolimus and deforolimus. mTOR inhibition has been studied in various solid tumors, including breast, gynecologic, gastrointestinal, prostate, lung, and head and neck cancers. Studies have focused on mTOR inhibition as a monotherapy or in combination with other drugs based on the principle that inhibiting as many targets as possible reduces the emergence of drug resistance. Temsirolimus is currently the only mTOR inhibitor that is specifically labeled for treatment of solid tumors. However, preclinical studies and early-phase trials are rapidly evolving. Additionally, research is further defining the complicated mTOR pathways and how they may be disordered in specific malignancies. To address these issues, NCCN convened a task force to review the underlying physiology of mTOR and related cellular pathways, and to review the current status of research of mTOR inhibition in solid tumors.
Figlin, Robert A Brown, Elizabeth Armstrong, Andrew J Akerley, Wallace Benson, Al B 3rd Burstein, Harold J Ettinger, David S Febbo, Phillip G Fury, Matthew G Hudes, Gary R Kies, Merrill S Kwak, Eunice L Morgan, Robert J Jr Mortimer, Joanne Reckamp, Karen Venook, Alan P Worden, Frank Yen, Yun Review United States Journal of the National Comprehensive Cancer Network : JNCCN J Natl Compr Canc Netw. 2008 Sep;6 Suppl 5:S1-S20; quiz S21-S22.