The Role of mTOR Signaling as a Therapeutic Target in Cancer

被引：208
作者：
Popova, Nadezhda V. [1 ]
Juecker, Manfred [2 ]
机构：
[1] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Lab Receptor Cell Biol, Miklukho Maklaya Str 16-10, Moscow 117997, Russia
[2] Univ Med Ctr Hamburg Eppendorf, Inst Biochem & Signal Transduct, Martinistr 52, D-20246 Hamburg, Germany
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2021年 / 22卷 / 04期
关键词：
mTOR; PI3K; AKT; cancer; mutation; therapy;
D O I：
10.3390/ijms22041743
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The aim of this review was to summarize current available information about the role of phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling in cancer as a potential target for new therapy options. The mTOR and PI3K/AKT/mTORC1 (mTOR complex 1) signaling are critical for the regulation of many fundamental cell processes including protein synthesis, cell growth, metabolism, survival, catabolism, and autophagy, and deregulated mTOR signaling is implicated in cancer, metabolic dysregulation, and the aging process. In this review, we summarize the information about the structure and function of the mTOR pathway and discuss the mechanisms of its deregulation in human cancers including genetic alterations of PI3K/AKT/mTOR pathway components. We also present recent data regarding the PI3K/AKT/mTOR inhibitors in clinical studies and the treatment of cancer, as well the attendant problems of resistance and adverse effects.
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页码：1 / 30
页数：27
相关论文
共 185 条
[1]   Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B alpha [J].
Alessi, DR ;
James, SR ;
Downes, CP ;
Holmes, AB ;
Gaffney, PRJ ;
Reese, CB ;
Cohen, P .
CURRENT BIOLOGY, 1997, 7 (04) :261-269
[2]   ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics [J].
Arteaga, Carlos L. ;
Engelman, Jeffrey A. .
CANCER CELL, 2014, 25 (03) :282-303
[3]   Ca2+- and phospholipase D-dependent and -independent pathways activate mTOR signaling [J].
Ballou, LM ;
Jiang, YP ;
Du, GW ;
Frohman, MA ;
Lin, RZ .
FEBS LETTERS, 2003, 550 (1-3) :51-56
[4]   EGFR gene amplification in breast cancer:: correlation with epidermal growth factor receptor mRNA and protein expression and HER-2 status and absence of EGFR-activating mutations [J].
Bhargava, R ;
Gerald, WL ;
Li, AR ;
Pan, QL ;
Lal, P ;
Ladanyi, M ;
Chen, BY .
MODERN PATHOLOGY, 2005, 18 (08) :1027-1033
[5]   Inhibition of 4EBP phosphorylation mediates the cytotoxic effect of mechanistic target of rapamycin kinase inhibitors in aggressive B-cell lymphomas [J].
Bi, Chengfeng ;
Zhang, Xuan ;
Lu, Ting ;
Zhang, Xiaoyan ;
Wang, Xianhuo ;
Meng, Bin ;
Zhang, Huilai ;
Wang, Ping ;
Vose, Julie M. ;
Chan, Wing C. ;
McKeithan, Timothy W. ;
Fu, Kai .
HAEMATOLOGICA, 2017, 102 (04) :755-764
[6]   2 DISTINCT SIGNAL TRANSMISSION PATHWAYS IN LYMPHOCYTES-T ARE INHIBITED BY COMPLEXES FORMED BETWEEN AN IMMUNOPHILIN AND EITHER FK506 OR RAPAMYCIN [J].
BIERER, BE ;
MATTILA, PS ;
STANDAERT, RF ;
HERZENBERG, LA ;
BURAKOFF, SJ ;
CRABTREE, G ;
SCHREIBER, SL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (23) :9231-9235
[7]   AKT1E17K in human solid tumours [J].
Bleeker, F. E. ;
Felicioni, L. ;
Buttitta, F. ;
Lamba, S. ;
Cardone, L. ;
Rodolfo, M. ;
Scarpa, A. ;
Leenstra, S. ;
Frattini, M. ;
Barbareschi, M. ;
Del Grammastro, M. ;
Sciarrotta, M. G. ;
Zanon, C. ;
Marchetti, A. ;
Bardelli, A. .
ONCOGENE, 2008, 27 (42) :5648-5650
[8]   Regulation of mTORC1 by growth factors, energy status, amino acids and mechanical stimuli at a glance [J].
Bond, Peter .
JOURNAL OF THE INTERNATIONAL SOCIETY OF SPORTS NUTRITION, 2016, 13
[9]  
Bonneau D, 2000, HUM MUTAT, V16, P109, DOI 10.1002/1098-1004(200008)16:2<109::AID-HUMU3>3.0.CO
[10]  
2-0
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