学术探索
学术期刊
新闻热点
数据分析
智能评审

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
收藏
页码：550 / 562
页数：13
相关论文
共 160 条
  • [31] Phosphatidylinositol 3-Kinase Hyperactivation Results in Lapatinib Resistance that Is Reversed by the mTOR/Phosphatidylinositol 3-Kinase Inhibitor NVP-BEZ235
    Eichhorn, Pieter J. A.
    Gili, Magui
    Scaltriti, Maurizio
    Serra, Violeta
    Guzman, Marta
    Nijkamp, Wouter
    Beijersbergen, Roderick L.
    Valero, Vanesa
    Seoane, Joan
    Bernards, Rene
    Baselga, Jose
    [J]. CANCER RESEARCH, 2008, 68 (22) : 9221 - 9230
  • [32] ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive non-small cell lung cancer cell lines
    Engelman, JA
    Jänne, PA
    Mermel, C
    Pearlberg, J
    Mukohara, T
    Fleet, C
    Cichowski, K
    Johnson, BE
    Cantley, LC
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (10) : 3788 - 3793
  • [33] Acquired resistance to tyrosine kinase inhibitors during cancer therapy
    Engelman, Jeffrey A.
    Settleman, Jeffrey
    [J]. CURRENT OPINION IN GENETICS & DEVELOPMENT, 2008, 18 (01) : 73 - 79
  • [34] Mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer
    Engelman, Jeffrey A.
    Jaenne, Pasi A.
    [J]. CLINICAL CANCER RESEARCH, 2008, 14 (10) : 2895 - 2899
  • [35] MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling
    Engelman, Jeffrey A.
    Zejnullahu, Kreshnik
    Mitsudomi, Tetsuya
    Song, Youngchul
    Hyland, Courtney
    Park, Joon Oh
    Lindeman, Neal
    Gale, Christopher-Michael
    Zhao, Xiaojun
    Christensen, James
    Kosaka, Takayuki
    Holmes, Alison J.
    Rogers, Andrew M.
    Cappuzzo, Federico
    Mok, Tony
    Lee, Charles
    Johnson, Bruce E.
    Cantley, Lewis C.
    Janne, Pasi A.
    [J]. SCIENCE, 2007, 316 (5827) : 1039 - 1043
  • [36] Allelic dilution obscures detection of a biologically significant resistance mutation in EGFR-amplified lung cancer
    Engelman, Jeffrey A.
    Mukohara, Toru
    Zejnullahu, Kreshnik
    Lifshits, Eugene
    Borras, Ana M.
    Gale, Christopher-Michael
    Naumov, George N.
    Yeap, Beow Y.
    Jarrell, Emily
    Sun, Jason
    Tracy, Sean
    Zhao, Xiaojun
    Heymach, John V.
    Johnson, Bruce E.
    Cantley, Lewis C.
    Janne, Pasi A.
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (10) : 2695 - 2706
  • [37] The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism
    Engelman, Jeffrey A.
    Luo, Ji
    Cantley, Lewis C.
    [J]. NATURE REVIEWS GENETICS, 2006, 7 (08) : 606 - 619
  • [38] Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers
    Engelman, Jeffrey A.
    Chen, Liang
    Tan, Xiaohong
    Crosby, Katherine
    Guimaraes, Alexander R.
    Upadhyay, Rabi
    Maira, Michel
    McNamara, Kate
    Perera, Samanthi A.
    Song, Youngchul
    Chirieac, Lucian R.
    Kaur, Ramneet
    Lightbown, Angela
    Simendinger, Jessica
    Li, Timothy
    Padera, Robert F.
    Garcia-Echeverria, Carlos
    Weissleder, Ralph
    Mahmood, Umar
    Cantley, Lewis C.
    Wong, Kwok-Kin
    [J]. NATURE MEDICINE, 2008, 14 (12) : 1351 - 1356
  • [39] A dual phosphoinositide-3-kinase α/mTOR inhibitor cooperates with blockade of epidermal growth factor receptor in PTEN-mutant glioma
    Fan, Qi-Wen
    Cheng, Christine K.
    Nicolaides, Theodore P.
    Hackett, Christopher S.
    Knight, Zachary A.
    Shokat, Kevan M.
    Weiss, William A.
    [J]. CANCER RESEARCH, 2007, 67 (17) : 7960 - 7965
  • [40] mTOR inhibitors in the treatment of cancer
    Fasolo, Angelica
    Sessa, Cristiana
    [J]. EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2008, 17 (11) : 1717 - 1734
12345678910