mTOR and cancer: insights into a complex relationship

被引:1111
作者
Sabatini, David M. [1 ]
机构
[1] MIT, Whitehead Inst Biomed Res, Dept Biol, Cambridge, MA 02142 USA
关键词
D O I
10.1038/nrc1974
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
mTOR (mammalian target of rapamycin) has come a long way since its humble beginnings as a kinase of unknown function. As part of the mTORC1 and mTORC2 complexes mTOR has key roles in several pathways that are involved in human cancer, stimulating interest in mTOR inhibitors and placing it on the radar of the pharmaceutical industry. Here, I discuss the rationale for the use of drugs that target mTOR, the unexpectedly complex mechanism of action of existing mTOR inhibitors and the potential benefits of developing drugs that function through different mechanisms. The purpose is not to cover all aspects of mTOR history and signalling, but rather to foster discussion by presenting some occasionally provocative ideas.
引用
收藏
页码:729 / 734
页数:6
相关论文
共 93 条
[61]  
PHUNG TL, IN PRESS CANC CELL
[62]   An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice [J].
Podsypanina, K ;
Lee, RT ;
Politis, C ;
Hennessy, I ;
Crane, A ;
Puc, J ;
Neshat, M ;
Wang, H ;
Yang, L ;
Gibbons, J ;
Frost, P ;
Dreisbach, V ;
Blenis, J ;
Gaciong, Z ;
Fisher, P ;
Sawyers, C ;
Hedrick-Ellenson, L ;
Parsons, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (18) :10320-10325
[63]   Akt regulates growth by directly phosphorylating Tsc2 [J].
Potter, CJ ;
Pedraza, LG ;
Xu, T .
NATURE CELL BIOLOGY, 2002, 4 (09) :658-665
[64]  
RUDELIUS M, 2006, BLOOD 0427, DOI DOI 10.1182/BLOOD-2006-04-015586
[65]   Novel role of the small GTPase Rheb: Its implication in endocytic pathway independent of the activation of mammalian target of rapamycin [J].
Saito, K ;
Araki, Y ;
Kontani, K ;
Nishina, H ;
Katada, T .
JOURNAL OF BIOCHEMISTRY, 2005, 137 (03) :423-430
[66]   Growing roles for the mTOR pathway [J].
Sarbassov, DD ;
Ali, SM ;
Sabatini, DM .
CURRENT OPINION IN CELL BIOLOGY, 2005, 17 (06) :596-603
[67]   Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB [J].
Sarbassov, DD ;
Ali, SM ;
Sengupta, S ;
Sheen, JH ;
Hsu, PP ;
Bagley, AF ;
Markhard, AL ;
Sabatini, DM .
MOLECULAR CELL, 2006, 22 (02) :159-168
[68]   Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex [J].
Sarbassov, DD ;
Guertin, DA ;
Ali, SM ;
Sabatini, DM .
SCIENCE, 2005, 307 (5712) :1098-1101
[69]   Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton [J].
Sarbassov, DD ;
Ali, SM ;
Kim, DH ;
Guertin, DA ;
Latek, RR ;
Erdjument-Bromage, H ;
Tempst, P ;
Sabatini, DM .
CURRENT BIOLOGY, 2004, 14 (14) :1296-1302
[70]   Rheb promotes cell growth as a component of the insulin/TOR signalling network [J].
Saucedo, LJ ;
Gao, XS ;
Chiarelli, DA ;
Li, L ;
Pan, D ;
Edgar, BA .
NATURE CELL BIOLOGY, 2003, 5 (06) :566-571