Targeting the mammalian target of rapamycin (mTOR): a new approach to treating cancer

被引:255
作者
Chan, S [1 ]
机构
[1] City Hosp, Nottingham NG5 1PB, England
关键词
PI3K pathway; PTEN; Akt; m-TOR; CCI-779; rapamycin;
D O I
10.1038/sj.bjc.6602162
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
mTOR is a downstream mediator in the PI3K/Akt signalling pathway, which plays a critical role in regulating basic cellular functions. These include cell proliferation, survival, mobility and angiogenesis. Rapamycin and its analogues (CCl-779, RAD001 and AP23573) have specific antagonistic action on the function of mTOR. This leads to inhibition of the downstream signalling elements and results in the cell cycle arrest in the G1 phase. This group of drugs may have a place in Oncology for the treatment of cancers, which occur as a result of increased activity of the PI3 kinase/Akt/m-TOR pathway. The basic structure of the pathway was reviewed in this article, together with results of the clinical studies targeting mTOR for cancer therapy. This is an exciting area for development and poses many challenges to researchers.
引用
收藏
页码:1420 / 1424
页数:5
相关论文
共 35 条
  • [1] Immunopharmacology of rapamycin
    Abraham, RT
    Wiederrecht, GJ
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 1996, 14 : 483 - 510
  • [2] ALEXANDRE J, 1999, P AACR NCI EORTC INT
  • [3] [Anonymous], AM SOC CLIN ONCOLOGY
  • [4] [Anonymous], M P AM SOC CLIN ONC
  • [5] PROGESTERONE-RECEPTOR REGULATION IN UTERINE CELLS - STIMULATION BY ESTROGEN, CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE, AND INSULIN-LIKE GROWTH FACTOR-I AND SUPPRESSION BY ANTIESTROGENS AND PROTEIN-KINASE INHIBITORS
    ARONICA, SM
    KATZENELLENBOGEN, BS
    [J]. ENDOCRINOLOGY, 1991, 128 (04) : 2045 - 2052
  • [6] ATKIN MB, 2002, M P AM SOC CLIN ONC, V21
  • [7] Barbe Esther, 1996, MEDITERR POLIT, V1, P25
  • [8] BASELGA J, 2004, M P AM SOC CLIN ONC, V23
  • [9] 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
  • [10] Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor α -: A new model for anti-estrogen resistance
    Campbell, RA
    Bhat-Nakshatri, P
    Patel, NM
    Constantinidou, D
    Ali, S
    Nakshatri, H
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (13) : 9817 - 9824