Hypoxia Promotes Resistance to EGFR Inhibition in NSCLC Cells via the Histone Demethylases, LSD1 and PLU-1

• Published in: Molecular cancer research Vol. 16; no. 10; pp. 1458 - 1469
• Main Authors: Lu, Yuhong, Liu, Yanfeng, Oeck, Sebastian, Glazer, Peter M.
• Format: Journal Article
• Language: English
• Published: United States 01.10.2018
• Subjects: Animals; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Cell Survival - drug effects; Drug Resistance, Neoplasm - genetics; Epithelial-Mesenchymal Transition - drug effects; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - genetics; Gefitinib - administration & dosage; Gene Expression Regulation, Neoplastic - drug effects; Histone Demethylases - antagonists & inhibitors; Histone Demethylases - genetics; Humans; Jumonji Domain-Containing Histone Demethylases - antagonists & inhibitors; Jumonji Domain-Containing Histone Demethylases - genetics; Mice; Mutation; Nuclear Proteins - antagonists & inhibitors; Nuclear Proteins - genetics; Protein Kinase Inhibitors - administration & dosage; Repressor Proteins - antagonists & inhibitors; Repressor Proteins - genetics; Tumor Hypoxia - drug effects; Xenograft Model Antitumor Assays

The development of small-molecule tyrosine kinase inhibitors (TKI) specific for epidermal growth factor receptors (EGFR) with activating mutations has led to a new paradigm in the treatment of non–small cell lung cancer (NSCLC) patients. However, most patients eventually develop resistance. Hypoxia...