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

[1] The mammalian target of rapamycin signaling pathway: Twists and turns in the road to cancer therapy
Abraham, Robert T.
Gibbons, James J.
[J]. CLINICAL CANCER RESEARCH, 2007, 13 (11) : 3109 - 3114
[2] Oncogenic PI3K deregulates transcription and translation
Bader, AG
Kang, SY
Zhao, L
Vogt, PK
[J]. NATURE REVIEWS CANCER, 2005, 5 (12) : 921 - 929
[3] mTOR Pathway and mTOR Inhibitors as Agents for Cancer Therapy
Baldo, Paolo
Cecco, Sara
Giacomin, Elisa
Lazzarini, Renzo
Rose, Barbara
Marastoni, Stefano
[J]. CURRENT CANCER DRUG TARGETS, 2008, 8 (08) : 647 - 665
[4] MOLECULAR ALTERATIONS OF THE AKT2 ONCOGENE IN OVARIAN AND BREAST CARCINOMAS
BELLACOSA, A
DEFEO, D
GODWIN, AK
BELL, DW
CHENG, JQ
ALTOMARE, DA
WAN, MH
DUBEAU, L
SCAMBIA, G
MASCIULLO, V
FERRANDINA, G
PANICI, PB
MANCUSO, S
NERI, G
TESTA, JR
[J]. INTERNATIONAL JOURNAL OF CANCER, 1995, 64 (04) : 280 - 285
[5] A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer
Berns, Katrien
Horlings, Hugo M.
Hennessy, Bryan T.
Madiredjo, Mandy
Hijmans, E. Marielle
Beelen, Karin
Linn, Sabine C.
Gonzalez-Angulo, Ana Maria
Stemke-Hale, Katherine
Hauptmann, Michael
Beijersbergen, Roderick L.
Mills, Gordon B.
de Vijver, Marc J. van
Bernards, Rene
[J]. CANCER CELL, 2007, 12 (04) : 395 - 402
[6] Proliferative defect and embryonic lethality in mice homozygous for a deletion in the p110α subunit of phosphoinositide 3-kinase
Bi, L
Okabe, I
Bernard, DJ
Wynshaw-Boris, A
Nussbaum, RL
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (16) : 10963 - 10968
[7] Early embryonic lethality in mice deficient in the p110β catalytic subunit of PI 3-kinase
Bi, L
Okabe, I
Bernard, DJ
Nussbaum, RL
[J]. MAMMALIAN GENOME, 2002, 13 (03) : 169 - 172
[8] Loss of PTEN/MMAC1/TEP in EGF receptor-expressing tumor cells counteracts the antitumor action of EGFR tyrosine kinase inhibitors
Bianco, R
Shin, I
Ritter, CA
Yakes, FM
Basso, A
Rosen, N
Tsurutani, J
Dennis, PA
Mills, GB
Arteaga, CL
[J]. ONCOGENE, 2003, 22 (18) : 2812 - 2822
[9] A selective inhibitor of the p110δ isoform of PI 3-kinase inhibits AML cell proliferation and survival and increases the cytotoxic effects of VP16
Billottet, C.
Grandage, V. L.
Gale, R. E.
Quattropani, A.
Rommel, C.
Vanhaesebroeck, B.
Khwaja, A.
[J]. ONCOGENE, 2006, 25 (50) : 6648 - 6659
[10] Inhibition of Class I Phosphoinositide 3-Kinase Activity Impairs Proliferation and Triggers Apoptosis in Acute Promyelocytic Leukemia without Affecting Atra-Induced Differentiation
Billottet, Clotilde
Banerjee, Lalita
Vanhaesebroeck, Bart
Khwaja, Asim
[J]. CANCER RESEARCH, 2009, 69 (03) : 1027 - 1036

← 1 2 3 4 5 6 7 8 9 10 →