Targeting enhancer reprogramming to mitigate MEK inhibitor resistance in preclinical models of advanced ovarian cancer

• Published in: The Journal of clinical investigation Vol. 131; no. 20; pp. 1 - 15
• Main Authors: Liu, Shini, Zou, Qiong, Chen, Jie-Ping, Yao, Xiaosai, Guan, Peiyong, Liang, Weiting, Deng, Peng, Lai, Xiaowei, Yin, Jiaxin, Chen, Jinghong, Chen, Rui, Yu, Zhaoliang, Xiao, Rong, Sun, Yichen, Hong, Jing Han, Liu, Hui, Lu, Huaiwu, Chen, Jianfeng, Bei, Jin-Xin, Koh, Joanna, Chan, Jason Yongsheng, Wang, Baohua, Kang, Tiebang, Yu, Qiang, Teh, Bin-Tean, Liu, Jihong, Xiong, Ying, Tan, Jing
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 15.10.2021
• Subjects: Animal models; Animals; Antitumor activity; Biomedical research; Cancer therapies; Cell Line, Tumor; Cellular signal transduction; Colorectal cancer; Disease Models, Animal; Drug dosages; Drug resistance; Drug Resistance, Neoplasm; Drug targeting; Drug therapy; Enhancer Elements, Genetic; Enzyme inhibitors; Epigenetic inheritance; Epigenetics; Extracellular signal-regulated kinase; Female; Gene amplification; Genetic aspects; Health aspects; Histone deacetylase; Histone Deacetylase Inhibitors - pharmacology; Humans; Inhibitor drugs; Kinases; MAP kinase; MAP Kinase Signaling System - physiology; MEK inhibitors; Melanoma; Mice; Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors; Mitogen-activated protein kinases; Mutation; Ovarian cancer; Ovarian Neoplasms - drug therapy; Patients; Pharmacology, Experimental; Phosphorylation; Protein kinase; Protein Kinase Inhibitors - therapeutic use; Proteins; Pyridones - pharmacology; Pyrimidinones - pharmacology; Targeted cancer therapy; Xenografts; China; Oncology; Molecular biology; Cancer; Drug screens

Ovarian cancer is characterized by aberrant activation of the mitogen-activated protein kinase (MAPK), highlighting the importance of targeting the MAPK pathway as an attractive therapeutic strategy. However, the clinical efficacy of MEK inhibitors is limited by intrinsic or acquired drug resistance...