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
[41]   Downregulation of MYCN through PI3K inhibition in mouse models of pediatric neural cancer [J].
Cage, Tene Aneka ;
Chanthery, Yvan ;
Chesler, Louis ;
Grimmer, Matthew ;
Knight, Zachary ;
Shokat, Kevan ;
Weiss, William A. ;
Gustafson, W. Clay .
FRONTIERS IN ONCOLOGY, 2015, 5
[42]   Inhibition of the PI3K Pathway Suppresses Hormonal Secretion and Limits Growth in Pheochromocytoma Cells [J].
Adler, Joel T. ;
Hottinger, Daniel G. ;
Kunnimalaiyaan, Muthusamy ;
Chen, Herbert .
WORLD JOURNAL OF SURGERY, 2009, 33 (11) :2452-2457
[43]   Combined inhibition of the PI3K/mTOR/MEK pathway induces Bim/Mcl-2-regulated apoptosis in pancreatic cancer cells [J].
Burmi, Rajpal S. ;
Maginn, Elaina N. ;
Gabra, Hani ;
Stronach, Euan A. ;
Wasan, Harpreet S. .
CANCER BIOLOGY & THERAPY, 2019, 20 (01) :21-30
[44]   Dual Inhibition of PI3K/AKT and MEK/ERK Pathways Induces Synergistic Antitumor Effects in Diffuse Intrinsic Pontine Glioma Cells [J].
Wu, Y. Linda ;
Maachani, Uday Bhanu ;
Schweitzer, Melanie ;
Singh, Ranjodh ;
Wang, Melinda ;
Chang, Raymond ;
Souweidane, Mark M. .
TRANSLATIONAL ONCOLOGY, 2017, 10 (02) :221-228
[45]   Preclinical evaluation of the CDK4/6 inhibitor palbociclib in combination with a PI3K or MEK inhibitor in colorectal cancer [J].
Lee, Cha Len ;
Cremona, Mattia ;
Farrelly, Angela ;
Workman, Julie A. ;
Kennedy, Sean ;
Aslam, Razia ;
Carr, Aoife ;
Madden, Stephen ;
O'Neill, Brian ;
Hennessy, Bryan T. ;
Toomey, Sinead .
CANCER BIOLOGY & THERAPY, 2023, 24 (01)
[46]   Targeting PI3K/mTOR signaling in cancer [J].
Arcaro, Alexandre .
FRONTIERS IN ONCOLOGY, 2014, 4
[47]   Plasma Metabolomic Changes following PI3K Inhibition as Pharmacodynamic Biomarkers: Preclinical Discovery to Phase I Trial Evaluation [J].
Ang, Joo Ern ;
Pandher, Rupinder ;
Ang, Joo Chew ;
Asad, Yasmin J. ;
Henley, Alan T. ;
Valenti, Melanie ;
Box, Gary ;
Brandon, Alexis de Haven ;
Baird, Richard D. ;
Friedman, Lori ;
Derynck, Mika ;
Vanhaesebroeck, Bart ;
Eccles, Suzanne A. ;
Kaye, Stan B. ;
Workman, Paul ;
de Bono, Johann S. ;
Raynaud, Florence I. .
MOLECULAR CANCER THERAPEUTICS, 2016, 15 (06) :1412-1424
[48]   The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches [J].
De Luca, Antonella ;
Maiello, Monica R. ;
D'Alessio, Amelia ;
Pergameno, Maria ;
Normanno, Nicola .
EXPERT OPINION ON THERAPEUTIC TARGETS, 2012, 16 :S17-S27
[49]   Increased activation of PI3K/AKT signaling pathway is associated with cholangiocarcinoma metastasis and PI3K/mTOR inhibition presents a possible therapeutic strategy [J].
Yothaisong, Supak ;
Dokduang, Hasaya ;
Techasen, Anchalee ;
Namwat, Nisana ;
Yongvanit, Puangrat ;
Bhudhisawasdi, Vajarabhongsa ;
Puapairoj, Anucha ;
Riggins, Gregory J. ;
Loilome, Watcharin .
TUMOR BIOLOGY, 2013, 34 (06) :3637-3648
[50]   Discovery of MEK/PI3K dual inhibitor via structure-based virtual screening [J].
Park, Hwangseo ;
Lee, Soyoung ;
Hong, Sungwoo .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (15) :4946-4950