From Rapa Nui to rapamycin: targeting PI3K/Akt/mTOR for cancer therapy

被引:55
作者
Georgakis, Georgios V. [1 ]
Younes, Anas [1 ]
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA
关键词
AP23573; apoptosis; CCI-779; cell cycle; lymphoma; RAD001;
D O I
10.1586/14737140.6.1.131
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
One of the most prominent pathways explored in the area of targeted therapy is the PI3K/Akt/mTOR pathway, which plays a central role in cell survival and proliferation. Deregulation of this pathway has been implicated in the promotion of cancer cell growth and survival. Inhibition of several steps of this pathway has been shown to confer favorable antitumor activity in a variety of cancer types. This article provides a brief analysis of the PI3K/Akt/mTOR pathway, its importance in tumor pathogenesis and the current status of preclinical and clinical studies targeting signaling components of this pathway.
引用
收藏
页码:131 / 140
页数:10
相关论文
共 87 条
[61]   Akt regulates growth by directly phosphorylating Tsc2 [J].
Potter, CJ ;
Pedraza, LG ;
Xu, T .
NATURE CELL BIOLOGY, 2002, 4 (09) :658-665
[62]  
POWIS G, 1994, CANCER RES, V54, P2419
[63]   Phosphorylation and activation of p70s6k by PDK1 [J].
Pullen, N ;
Dennis, PB ;
Andjelkovic, M ;
Dufner, A ;
Kozma, SC ;
Hemmings, BA ;
Thomas, G .
SCIENCE, 1998, 279 (5351) :707-710
[64]   Phosphorylation of PTP1B at Ser50 by Akt impairs its ability to dephosphorylate the insulin receptor [J].
Ravichandran, LV ;
Chen, H ;
Li, YH ;
Quon, MJ .
MOLECULAR ENDOCRINOLOGY, 2001, 15 (10) :1768-1780
[65]   Akt-dependent phosphorylation of p21Cip1 regulates PCNA binding and proliferation of endothelial cells [J].
Rössig, L ;
Jadidi, AS ;
Urbich, C ;
Badorff, C ;
Zeiher, AM ;
Dimmeler, S .
MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (16) :5644-5657
[66]   RAFT1 - A MAMMALIAN PROTEIN THAT BINDS TO FKBP12 IN A RAPAMYCIN-DEPENDENT FASHION AND IS HOMOLOGOUS TO YEAST TORS [J].
SABATINI, DM ;
ERDJUMENTBROMAGE, H ;
LUI, M ;
TEMPST, P ;
SNYDER, SH .
CELL, 1994, 78 (01) :35-43
[67]  
Sankhala KK, 2005, J CLIN ONCOL, V23, P9028
[68]   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
[69]   Will mTOR inhibitors make it as cancer drugs? [J].
Sawyers, CL .
CANCER CELL, 2003, 4 (05) :343-348
[70]   The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress [J].
Shaw, RJ ;
Kosmatka, M ;
Bardeesy, N ;
Hurley, RL ;
Witters, LA ;
DePinho, RA ;
Cantley, LC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (10) :3329-3335