Targeting PI3K signalling in cancer: opportunities, challenges and limitations

被引：2015

作者：

Engelman, Jeffrey A. ^{[1
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA

来源：

NATURE REVIEWS CANCER | 2009年 / 9卷 / 08期

基金：

美国国家卫生研究院;

关键词：

GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; TYROSINE KINASE INHIBITORS; TUMOR-SUPPRESSOR GENE; PHOSPHATIDYLINOSITOL 3-KINASE/MAMMALIAN TARGET; PHOSPHOINOSITIDE 3-KINASE/AKT PATHWAY; RICTOR-MTOR COMPLEX; ANTITUMOR-ACTIVITY; BREAST-CANCER; ACQUIRED-RESISTANCE;

D O I：

10.1038/nrc2664

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

There are ample genetic and laboratory studies that suggest the PI3K-Akt pathway is vital to the growth and survival of cancer cells. Inhibitors targeting this pathway are entering the clinic at a rapid pace. In this Review, the therapeutic potential of drugs targeting PI3K-Akt signalling for the treatment of cancer is discussed. I focus on the advantages and drawbacks of different treatment strategies for targeting this pathway, the cancers that might respond best to these therapies and the challenges and limitations that confront their clinical development.

引用

页码：550 / 562

页数：13

共 160 条

[61] The structure of a human p110α/p85α complex elucidates the effects of oncogenic PI3Kα mutations
Huang, Chuan-Hsiang
Mandelker, Diana
Schmidt-Kittler, Oleg
Samuels, Yardena
Velculescu, Victor E.
Kinzler, Kenneth W.
Vogelstein, Bert
Gabelli, Sandra B.
Amzel, L. Mario
[J]. SCIENCE, 2007, 318 (5857) : 1744 - 1748
[62] The TSC1-TSC2 complex: a molecular switchboard controlling cell growth
Huang, Jingxiang
Manning, Brendan D.
[J]. BIOCHEMICAL JOURNAL, 2008, 412 : 179 - 190
[63] Mutations in the Phosphatidylinositol-3-Kinase Pathway Predict for Antitumor Activity of the Inhibitor PX-866 whereas Oncogenic Ras Is a Dominant Predictor for Resistance
Ihle, Nathan T.
Lemos, Robert, Jr.
Wipf, Peter
Yacoub, Adly
Mitchell, Clint
Siwak, Doris
Mills, Gordon B.
Dent, Paul
Kirkpatrick, D. Lynn
Powis, Garth
[J]. CANCER RESEARCH, 2009, 69 (01) : 143 - 150
[64] Peroxisome proliferator-activated receptor γ agonist pioglitazone prevents the hyperglycemia caused by phosphatidylinositol 3-kinase pathway inhibition by PX-866 without affecting antitumor activity
Ihle, Nathan T.
Lemos, Robert
Schwartz, David
Oh, Junghwan
Halter, Robert J.
Wipf, Peter
Kirkpatrick, Lynn
Powis, Garth
[J]. MOLECULAR CANCER THERAPEUTICS, 2009, 8 (01) : 94 - 100
[65] Ihle NT, 2004, MOL CANCER THER, V3, P763
[66] TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
Inoki, K
Li, Y
Zhu, TQ
Wu, J
Guan, KL
[J]. NATURE CELL BIOLOGY, 2002, 4 (09) : 648 - 657
[67] Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling
Inoki, K
Li, Y
Xu, T
Guan, KL
[J]. GENES & DEVELOPMENT, 2003, 17 (15) : 1829 - 1834
[68] Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial-mesenchymal transition
Irie, HY
Pearline, RV
Grueneberg, D
Hsia, M
Ravichandran, P
Kothari, N
Natesan, S
Brugge, JS
[J]. JOURNAL OF CELL BIOLOGY, 2005, 171 (06) : 1023 - 1034
[69] SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity
Jacinto, Estela
Facchinetti, Valeria
Liu, Dou
Soto, Nelyn
Wei, Shiniu
Jung, Sung Yun
Huang, Qiaojia
Qin, Jun
Su, Bing
[J]. CELL, 2006, 127 (01) : 125 - 137
[70] Essential roles of PI(3)K-p110β in cell growth, metabolism and tumorigenesis
Shidong Jia
Zhenning Liu
Sen Zhang
Pixu Liu
Lei Zhang
Sang Hyun Lee
Jing Zhang
Sabina Signoretti
Massimo Loda
Thomas M. Roberts
Jean J. Zhao
[J]. Nature, 2008, 454 (7205) : 776 - 779

← 2 3 4 5 6 7 8 9 10 11 →