PI3K/Akt/mTOR pathway as a target for cancer therapy

被引:434
作者
Morgensztern, D
McLeod, HL
机构
[1] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Genet, St Louis Vet Adm Med Ctr, St Louis, MO USA
[3] Siteman Canc Ctr, St Louis, MO USA
关键词
genomics; mTOR; pAKT; PI3K; rapamycin; therapeutics;
D O I
10.1097/01.cad.0000173476.67239.3b
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The PI3K/Akt/mTOR pathway regulates several normal cellular functions that are also critical for tumorigenesis, including cellular proliferation, growth, survival and mobility. Components of this pathway are frequently abnormal in a variety of tumors, making them an attractive target for anti-cancer therapy. Inhibition of mTOR in patients with cancer became more feasible after the development of rapamycin analogs with improved pharmacologic properties. The promising activity of these agents in early clinical trials has led to the development of ongoing phase III trials in renal cell carcinoma and breast cancer. Future studies are needed to identify the patients most likely to benefit from this form of therapy, and to define its role in combination with chemotherapy, hormones and growth factor inhibitors.
引用
收藏
页码:797 / 803
页数:7
相关论文
共 70 条
[11]   Akt phosphorylation and gefitinib efficacy in patients with advanced non-small-cell lung cancer [J].
Cappuzzo, F ;
Magrini, E ;
Ceresoli, GL ;
Bartolini, S ;
Rossi, E ;
Ludovini, V ;
Gregorc, V ;
Ligorio, C ;
Cancellieri, A ;
Damiani, S ;
Spreafico, A ;
Paties, CT ;
Lombardo, L ;
Calandri, C ;
Bellezza, G ;
Tonato, M ;
Crinò, L .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2004, 96 (15) :1133-1141
[12]  
CHAN S, 2003, P AN M AM SOC CLIN, V22, P193
[13]   Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy [J].
Chang, F ;
Lee, JT ;
Navolanic, PM ;
Steelman, LS ;
Shelton, JG ;
Blalock, WL ;
Franklin, RA ;
McCubrey, JA .
LEUKEMIA, 2003, 17 (03) :590-603
[14]   AKT2, A PUTATIVE ONCOGENE ENCODING A MEMBER OF A SUBFAMILY OF PROTEIN-SERINE THREONINE KINASES, IS AMPLIFIED IN HUMAN OVARIAN CARCINOMAS [J].
CHENG, JQ ;
GODWIN, AK ;
BELLACOSA, A ;
TAGUCHI, T ;
FRANKE, TF ;
HAMILTON, TC ;
TSICHLIS, PN ;
TESTA, JR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (19) :9267-9271
[15]   Amplification of AKT2 in human pancreatic cancer cells and inhibition of ATK2 expression and tumorigenicity by antisense RNA [J].
Cheng, JQ ;
Ruggeri, B ;
Klein, WM ;
Sonoda, G ;
Altomare, DA ;
Watson, DK ;
Testa, JR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (08) :3636-3641
[16]   The 145-kDa protein induced to associate with Shc by multiple cytokines is an inositol tetraphosphate and phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase [J].
Damen, JE ;
Liu, L ;
Rosten, P ;
Humphries, RK ;
Jefferson, AB ;
Majerus, PW ;
Krystal, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (04) :1689-1693
[17]   Cellular survival: a play in three Akts [J].
Datta, SR ;
Brunet, A ;
Greenberg, ME .
GENES & DEVELOPMENT, 1999, 13 (22) :2905-2927
[18]   Mechanisms of androgen-refractory prostate cancer. [J].
Debes, JD ;
Tindall, DJ .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (15) :1488-1490
[19]   Reduced PTEN expression in breast cancer cells confers susceptibility to inhibitors of the PI3 kinase/Akt pathway [J].
deGraffenried, LA ;
Fulcher, L ;
Friedrichs, WE ;
Grünwald, V ;
Ray, RB ;
Hidalgo, M .
ANNALS OF ONCOLOGY, 2004, 15 (10) :1510-1516
[20]   Inhibition of mTOR activity restores tamoxifen response in breast cancer cells with aberrant Akt activity [J].
DeGraffenried, LA ;
Friedrichs, WE ;
Russell, DH ;
Donzis, EJ ;
Middleton, AK ;
Silva, JM ;
Roth, RA ;
Hidalgo, M .
CLINICAL CANCER RESEARCH, 2004, 10 (23) :8059-8067