The mammalian target of rapamycin signaling pathway: Twists and turns in the road to cancer therapy

被引:207
作者
Abraham, Robert T. [1 ]
Gibbons, James J. [1 ]
机构
[1] Wyeth, Dept Oncol Discovery, Pearl River, NY 10960 USA
关键词
D O I
10.1158/1078-0432.CCR-06-2798
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The immunosuppressive drug rapamycin played a key role in the functional characterization of mammalian target of rapamycin (mTOR), an unusual protein kinase that coordinates growth factor and nutrient availability with cell growth and proliferation. Several rapamycin-related compounds are now in various stages of clinical development as anticancer agents. This article highlights recent advances in our understanding of the mTOR signaling pathway and the implications of these findings for the clinical application of mTOR inhibitors in cancer patients.
引用
收藏
页码:3109 / 3114
页数:6
相关论文
共 73 条
  • [1] PI 3-kinase related kinases: 'big' players in stress-induced signaling pathways
    Abraham, RT
    [J]. DNA REPAIR, 2004, 3 (8-9) : 883 - 887
  • [2] Immunopharmacology of rapamycin
    Abraham, RT
    Wiederrecht, GJ
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 1996, 14 : 483 - 510
  • [3] ANSEL SM, 2006, J CLIN ONCOL S18S, V24, P7532
  • [4] Lack of PTEN expression in endometrial intraepithelial neoplasia is correlated with cancer progression
    Baak, JPA
    van Diermen, B
    Steinbakk, A
    Janssen, E
    Skaland, I
    Mutter, GL
    Fiane, B
    Lovslett, K
    [J]. HUMAN PATHOLOGY, 2005, 36 (05) : 555 - 561
  • [5] TOR controls translation initiation and early G1 progression in yeast
    Barbet, NC
    Schneider, U
    Helliwell, SB
    Stansfield, I
    Tuite, MF
    Hall, MN
    [J]. MOLECULAR BIOLOGY OF THE CELL, 1996, 7 (01) : 25 - 42
  • [6] A MAMMALIAN PROTEIN TARGETED BY G1-ARRESTING RAPAMYCIN-RECEPTOR COMPLEX
    BROWN, EJ
    ALBERS, MW
    SHIN, TB
    ICHIKAWA, K
    KEITH, CT
    LANE, WS
    SCHREIBER, SL
    [J]. NATURE, 1994, 369 (6483) : 756 - 758
  • [7] Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex
    Brugarolas, J
    Lei, K
    Hurley, RL
    Manning, BD
    Reiling, JH
    Hafen, E
    Witter, LA
    Ellisen, LW
    Kaelin, WG
    [J]. GENES & DEVELOPMENT, 2004, 18 (23) : 2893 - 2904
  • [8] hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase
    Byfield, MP
    Murray, JT
    Backer, JM
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (38) : 33076 - 33082
  • [9] Phase II study of CCI-779 in patients with recurrent glioblastoma multiforme
    Chang, SM
    Wen, P
    Cloughesy, T
    Greenberg, H
    Schiff, D
    Conrad, C
    Fink, K
    Robins, HI
    De Angelis, L
    Raizer, J
    Hess, K
    Aldape, K
    Lamborn, KR
    Kuhn, J
    Dancey, J
    Prados, MD
    [J]. INVESTIGATIONAL NEW DRUGS, 2005, 23 (04) : 357 - 361
  • [10] IDENTIFICATION OF AN 11-KDA FKBP12-RAPAMYCIN-BINDING DOMAIN WITHIN THE 289-KDA FKBP12-RAPAMYCIN-ASSOCIATED PROTEIN AND CHARACTERIZATION OF A CRITICAL SERINE RESIDUE
    CHEN, J
    ZHENG, XF
    BROWN, EJ
    SCHREIBER, SL
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (11) : 4947 - 4951