Inhibition of PI3K and MEK: It Is All about Combinations and Biomarkers

被引:33
|
作者
Rexer, Brent N.
Ghosh, Ritwik
Arteaga, Carlos L. [1 ]
机构
[1] Vanderbilt Univ, Sch Med, Div Oncol, Dept Med, Nashville, TN 37232 USA
关键词
CANCER; MTOR; ACTIVATION;
D O I
10.1158/1078-0432.CCR-09-0872
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
A small molecule inhibitor of MAP/ERK kinase (MEK) was effective against human breast cancer cells with a basal-like gene expression signature. Antitumor activity was limited by both feedback upregulation of phosphatidylinositol-3 kinase (PI3K)/AKT upon inhibition of MEK as well as loss of the phosphatase PTEN. Therefore, MEK inhibitors should preferably be investigated in combination with PI3K inhibitors in basal-like breast cancers. (Clin Cancer Res 2009;15(14) July 2009).
引用
收藏
页码:4518 / 4520
页数:3
相关论文
共 50 条
  • [31] Inhibition of mTOR, but not PI3K, is required for the anti-tumor efficacy in breast cancer of dual PI3K/mTOR inhibitors given in combination with MEK inhibitors
    Smith, Aleisha M.
    Xiong, Jessie
    Hunter, Lucas
    Jordan, Jamie
    Clark, Kelly
    Darr, David B.
    Norman, Sharpless
    Perou, Charles M.
    Kim, William Y.
    CANCER RESEARCH, 2015, 75
  • [32] Structural effects of morpholine replacement in ZSTK474 on Class I PI3K isoform inhibition: Development of novel MEK/PI3K bifunctional inhibitors
    Van Dort, Marcian E.
    Jang, Youngsoon
    Bonham, Christopher A.
    Heist, Kevin
    McDonald, Lucas
    Zhang, Edward Z.
    Chenevert, Thomas L.
    Luker, Gary D.
    Ross, Brian D.
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2022, 229
  • [33] Biomarkers for predicting response to PI3K inhibitors
    Cantley, Lewis C.
    CANCER RESEARCH, 2011, 71
  • [34] SYNERGY OF VENETOCLAX AND DUAL MTOR/PI3K INHIBITION IN BCP-ALL
    Niedermayer, Alexandra
    Enzenmueller, Stefanie
    Seyfried, Felix
    Debatin, Klaus-Michael
    Meyer, Lüder
    PEDIATRIC BLOOD & CANCER, 2022, 69
  • [35] Metabolic biomarkers for response to PI3K inhibition in basal-like breast cancer
    Siver A Moestue
    Cornelia G Dam
    Saurabh S Gorad
    Alexandr Kristian
    Anna Bofin
    Gunhild M Mælandsmo
    Olav Engebråten
    Ingrid S Gribbestad
    Geir Bjørkøy
    Breast Cancer Research, 15
  • [36] Metabolic biomarkers for response to PI3K inhibition in basal-like breast cancer
    Moestue, Siver A.
    Dam, Cornelia G.
    Gorad, Saurabh S.
    Kristian, Alexandr
    Bofin, Anna
    Maelandsmo, Gunhild M.
    Engebraten, Olav
    Gribbestad, Ingrid S.
    Bjorkoy, Geir
    BREAST CANCER RESEARCH, 2013, 15 (01):
  • [37] Synergistic Anticancer Efficacy of MEK Inhibition and Dual PI3K/mTOR Inhibition in Castration-Resistant Prostate Cancer
    Park, Hongzoo
    Kim, Yunlim
    Sul, Jee-Won
    Jeong, In Gab
    Yi, Hye-Jin
    Ahn, Jae Beom
    Kang, Jong Soon
    Yun, Jieun
    Hwang, Jung Jin
    Kim, Choung-Soo
    PROSTATE, 2015, 75 (15): : 1747 - 1759
  • [38] In pursuit of synergy: An investigation of the PI3K/mTOR/MEK co-targeted inhibition strategy in NSCLC
    Heavey, Susan
    Cuffe, Sinead
    Finn, Stephen
    Young, Vincent
    Ryan, Ronan
    Nicholson, Siobhan
    Leonard, Niamh
    McVeigh, Niall
    Barr, Martin
    O'Byrne, Kenneth
    Gately, Kathy
    ONCOTARGET, 2016, 7 (48) : 79512 - 79529
  • [39] The Role of PI3kγ and PI3kΔ in Alloimmunity
    Uehara, M.
    Jamil, A.
    Solhjou, Z.
    McGrath, M.
    Banouni, N.
    Evans, C.
    Dinitto, J.
    Winkler, D.
    Abdi, R.
    AMERICAN JOURNAL OF TRANSPLANTATION, 2016, 16 : 325 - 325
  • [40] The role of PI3kγ and PI3kδ in alloimmunity
    Uehara, Mayuko
    Jamil, Azzi
    Ohori, Shunsuke
    Solhjou, Zhabiz
    McGrath, Martina
    Banouni, Naima M.
    Evans, Catherine A.
    Dinitto, Jonathan P.
    Winkler, David G.
    Abdi, Reza
    TRANSPLANTATION, 2016, 100 (07) : S361 - S361