Targeting the PI3K/Akt/mTOR Pathway in Ocular Neovascularization

被引:38
作者
Sasore, Temitope [1 ]
Reynolds, Alison L. [1 ]
Kennedy, Breandan N. [1 ]
机构
[1] Univ Coll Dublin, Conway Inst, Sch Biomol & Biomed Sci, Dublin 4, Ireland
来源
RETINAL DEGENERATIVE DISEASES: MECHANISMS AND EXPERIMENTAL THERAPY | 2014年 / 801卷
关键词
Phosphoinositol 3 kinase (PI3K); Mammalian target of rapamycin (mTOR); Protein kinase B/Akt; Neovascularization; Blindness; Vascular endothelial growth factor (VEGF); ENDOTHELIAL GROWTH-FACTOR; PHOSPHOINOSITIDE; 3-KINASE; MEDIATES ANGIOGENESIS; EXPRESSION; INHIBITOR;
D O I
10.1007/978-1-4614-3209-8_101
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Ocular neovascularization, a common pathological feature of wet age-related macular degeneration (AMD), proliferative and diabetic retinopathy (PDR) leads to fluid and blood leakage, scar formation and ultimately blindness. Elucidation of vascular endothelial growth factor (VEGF) as a key mediator of angiogenesis led to clinically approved anti-VEGF agents. However, these drugs are associated with adverse side-effects, high costs and extensive clinical burden. The phosphatidylinositol-3-kinase (PI3K) pathway is an alternative therapeutic target in angiogenic diseases. The PI3K/Akt/mTOR pathway orchestrates an array of normal cellular processes, including growth, survival and angiogenesis. Here, we review the potential of targeting the PI3K pathway, to treat ocular neovascularization.
引用
收藏
页码:805 / 811
页数:7
相关论文
共 31 条
[1]   Selective Inhibition of Retinal Angiogenesis by Targeting PI3 Kinase [J].
Alvarez, Yolanda ;
Astudillo, Olaya ;
Jensen, Lasse ;
Reynolds, Alison L. ;
Waghorne, Nora ;
Brazil, Derek P. ;
Cao, Yihai ;
O'Connor, John J. ;
Kennedy, Breandan N. .
PLOS ONE, 2009, 4 (11)
[2]   Altered VEGF mRNA Stability following Treatments with Immunosuppressive Agents IMPLICATIONS FOR CANCER DEVELOPMENT [J].
Basu, Aninda ;
Datta, Dipak ;
Zurakowski, David ;
Pal, Soumitro .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (33) :25196-25202
[3]   Activation of vascular endothelial growth factor receptor-1 sustains angiogenesis and bcl-2 expression via the phosphatidylinositol 3-kinase pathway in endothelial cells [J].
Cai, J ;
Ahmad, S ;
Jiang, WG ;
Huang, JH ;
Kontos, CD ;
Boulton, M ;
Ahmed, A .
DIABETES, 2003, 52 (12) :2959-2968
[4]   Targeted pharmacotherapy of retinal diseases with ranibizumab [J].
Campochiaro, Peter A. .
DRUGS OF TODAY, 2007, 43 (08) :529-537
[5]   The phosphoinositide 3-kinase pathway [J].
Cantley, LC .
SCIENCE, 2002, 296 (5573) :1655-1657
[6]   Combination angiostatic therapy completely inhibits ocular and tumor angiogenesis [J].
Dorrell, Michael I. ;
Aguilar, Edith ;
Scheppke, Lea ;
Barnett, Faith H. ;
Friedlander, Martin .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (03) :967-972
[7]   The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism [J].
Engelman, Jeffrey A. ;
Luo, Ji ;
Cantley, Lewis C. .
NATURE REVIEWS GENETICS, 2006, 7 (08) :606-619
[8]   NVP-BYL719, a novel PI3Kalpha selective inhibitor with all the characteristics required for clinical development as an anti-cancer agent [J].
Fritsch, Christine M. ;
Schnell, Christian ;
Chatenay-Rivauday, Christian ;
Guthy, Daniel A. ;
De Pover, Alain ;
Wartmann, Markus ;
Brachmann, Saskia ;
Maira, Sauveur-Michel ;
Huang, Alan ;
Quadt, Cornelia ;
Hofmann, Francesco ;
Caravatti, Giorgio .
CANCER RESEARCH, 2012, 72
[9]   Phosphoinositide kinases [J].
Fruman, DA ;
Meyers, RE ;
Cantley, LC .
ANNUAL REVIEW OF BIOCHEMISTRY, 1998, 67 :481-507
[10]   Tipping the balance for angiogenic disorders [J].
Gao, GQ ;
Ma, JX .
DRUG DISCOVERY TODAY, 2002, 7 (03) :171-172