Taming the PI3K team to hold inflammation and cancer at bay

被引:81
作者
Hirsch, Emilio [1 ]
Ciraolo, Elisa [1 ]
Ghigo, Alessandra [1 ]
Costa, Carlotta [1 ]
机构
[1] Univ Turin, Ctr Mol Biotechnol, I-10126 Turin, Italy
关键词
signal transduction; PI3K; cancer; inflammation; kinase inhibitors;
D O I
10.1016/j.pharmthera.2008.02.004
中图分类号
R9 [药学];
学科分类号
1007 [药学];
摘要
Recent progress in understanding the molecular mechanisms of receptor signal transduction is continuously highlighting new unforeseen potential drug targets for yet unmet therapeutic needs. While the large number of different cell surface receptors challenge the concept of antagonists development, the finding of signal transduction platforms common to multiple receptor families has boosted the development of new therapeutic approaches. The identification of the role of phosphomositide 3-kinase family members downstream receptors as directors of multiple cellular responses ranging from cell proliferation and survival to immunity and cardiovascular control, is an example of successful drug target validation studies. This review will focus on these findings and on the ongoing efforts to tame this family of enzymes to beat inflammation and cancer. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:192 / 205
页数:14
相关论文
共 156 条
[1]
Requirement for phosphoinositide 3-kinase p110δ signaling in B cell antigen receptor-mediated antigen presentation [J].
Al-Alwan, Monther M. ;
Okkenhaug, Klaus ;
Vanhaesebroeck, Bart ;
Hayflick, Joel S. ;
Marshall, Aaron J. .
JOURNAL OF IMMUNOLOGY, 2007, 178 (04) :2328-2335
[2]
Phosphoinositide 3-kinase γ participates in T cell receptor-induced T cell activation [J].
Alcázar, Isabela ;
Marqués, Miriam ;
Kumar, Amit ;
Hirsch, Emilio ;
Wymann, Matthias ;
Carrera, Ana C. ;
Barber, Domingo F. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (12) :2977-2987
[3]
Essential role for the p110δ phosphoinositide 3-kinase in the allergic response [J].
Ali, K ;
Bilancio, A ;
Thomas, M ;
Pearce, W ;
Gilfillan, AM ;
Tkaczyk, C ;
Kuehn, N ;
Gray, A ;
Giddings, J ;
Peskett, E ;
Fox, R ;
Bruce, I ;
Walker, C ;
Sawyer, C ;
Okkenhaug, K ;
Finan, P ;
Vanhaesebroeck, B .
NATURE, 2004, 431 (7011) :1007-1011
[4]
WORTMANNIN IS A POTENT PHOSPHATIDYLINOSITOL 3-KINASE INHIBITOR - THE ROLE OF PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE IN NEUTROPHIL RESPONSES [J].
ARCARO, A ;
WYMANN, MP .
BIOCHEMICAL JOURNAL, 1993, 296 :297-301
[5]
Early onset of neoplasia in the prostate and skin of mice with tissue-specific deletion of Pten [J].
Backman, SA ;
Ghazarian, D ;
So, K ;
Sanchez, O ;
Wagner, KU ;
Hennighausen, L ;
Suzuki, A ;
Tsao, MS ;
Chapman, WB ;
Stambolic, V ;
Mak, TW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (06) :1725-1730
[6]
Cancer-specific mutations in PIK3CA are oncogenic in vivo [J].
Bader, AG ;
Kang, SY ;
Vogt, PK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (05) :1475-1479
[7]
Oncogenic PI3K deregulates transcription and translation [J].
Bader, AG ;
Kang, SY ;
Zhao, L ;
Vogt, PK .
NATURE REVIEWS CANCER, 2005, 5 (12) :921-929
[8]
Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38 [J].
Bai, Xiaochun ;
Ma, Dongzhu ;
Liu, Anling ;
Shen, Xiaoyun ;
Wang, Qiming J. ;
Liu, Yongjian ;
Jiang, Yu .
SCIENCE, 2007, 318 (5852) :977-980
[9]
PI3Kγ inhibition blocks glomerulonephritis and extends lifespan in a mouse model of systemic lupus [J].
Barber, DF ;
Bartolomé, A ;
Hernandez, C ;
Flores, JM ;
Redondo, C ;
Fernandez-Arias, C ;
Camps, M ;
Ruckle, T ;
Schwarz, MK ;
Rodríguez, S ;
Martinez-A, C ;
Balomenos, D ;
Rommel, C ;
Carrera, AC .
NATURE MEDICINE, 2005, 11 (09) :933-935
[10]
A specific function for phosphatidylinositol 3-kinase α (p85α-p110α) in cell survival and for phosphatidylinositol 3-kinase β (p85α-p110β) in de novo DNA synthesis of human colon carcinoma cells [J].
Bénistant, C ;
Chapuis, H ;
Roche, S .
ONCOGENE, 2000, 19 (44) :5083-5090