scholarly journals Inhibitory Effects of the Mitogen-Activated Protein Kinase Kinase Inhibitor CI-1040 on the Proliferation and Tumor Growth of Thyroid Cancer Cells withBRAForRASMutations

2007 ◽  
Vol 92 (12) ◽  
pp. 4686-4695 ◽  
Author(s):  
Dingxie Liu ◽  
Zhi Liu ◽  
David Jiang ◽  
Alan P. Dackiw ◽  
Mingzhao Xing
Keyword(s):  
Thyroid Cancer ◽  
Protein Kinase ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Kinase Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Inhibitory Effects ◽  
Mitogen Activated Protein ◽  
Thyroid Cancer Cells ◽  
Protein Kinase Kinase

scholarly journals Local Anesthetics Induce Apoptosis in Human Thyroid Cancer Cells through the Mitogen-Activated Protein Kinase Pathway

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e89563 ◽  
Author(s):  
Yuan-Ching Chang ◽  
Yi-Chiung Hsu ◽  
Chien-Liang Liu ◽  
Shih-Yuan Huang ◽  
Meng-Chun Hu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Local Anesthetics ◽  
Mitogen Activated Protein Kinase ◽  
Human Thyroid ◽  
Mitogen Activated Protein ◽  
Thyroid Cancer Cells ◽  
Kinase Pathway

scholarly journals ZEB1 suppression sensitizes KRAS mutant cancers to MEK inhibition by an IL17RD-dependent mechanism

2019 ◽  
Vol 11 (483) ◽  
pp. eaaq1238 ◽  
Author(s):  
David H. Peng ◽  
Samrat T. Kundu ◽  
Jared J. Fradette ◽  
Lixia Diao ◽  
Pan Tong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Protein Kinase ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Mapk Signaling ◽  
Lung Tumors ◽  
Mitogen Activated Protein Kinase ◽  
Mek Inhibition ◽  
Mitogen Activated Protein

Mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitors have failed to show clinical benefit in Kirsten rat sarcoma (KRAS) mutant lung cancer due to various resistance mechanisms. To identify differential therapeutic sensitivities between epithelial and mesenchymal lung tumors, we performed in vivo small hairpin RNA screens, proteomic profiling, and analysis of patient tumor datasets, which revealed an inverse correlation between mitogen-activated protein kinase (MAPK) signaling dependency and a zinc finger E-box binding homeobox 1 (ZEB1)–regulated epithelial-to-mesenchymal transition. Mechanistic studies determined that MAPK signaling dependency in epithelial lung cancer cells is due to the scaffold protein interleukin-17 receptor D (IL17RD), which is directly repressed by ZEB1. Lung tumors in multiple Kras mutant murine models with increased ZEB1 displayed low IL17RD expression, accompanied by MAPK-independent tumor growth and therapeutic resistance to MEK inhibition. Suppression of ZEB1 function with miR-200 expression or the histone deacetylase inhibitor mocetinostat sensitized resistant cancer cells to MEK inhibition and markedly reduced in vivo tumor growth, showing a promising combinatorial treatment strategy for KRAS mutant cancers. In human lung tumor samples, high ZEB1 and low IL17RD expression correlated with low MAPK signaling, presenting potential markers that predict patient response to MEK inhibitors.

scholarly journals Activity of the oral mitogen-activated protein kinase kinase inhibitor trametinib inRAS-mutant relapsed or refractory myeloid malignancies

Cancer ◽  
2016 ◽  
Vol 122 (12) ◽  
pp. 1871-1879 ◽  
Author(s):  
Gautam Borthakur ◽  
Leslie Popplewell ◽  
Michael Boyiadzis ◽  
James Foran ◽  
Uwe Platzbecker ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Myeloid Malignancies ◽  
Mitogen Activated Protein ◽  
Protein Kinase Kinase
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