Targeted therapy of esophageal squamous cell carcinoma: the NRF2 signaling pathway as target

Annals of the New York Academy of Sciences
Shaohua MaXiaoxin Luke Chen

Abstract

Esophageal squamous cell carcinoma (ESCC) is a deadly disease that requires extensive research. Here, we review the current understanding of the functions of the nuclear factor erythroid-derived 2-like 2 (NRF2) signaling pathway in the esophagus. Genomic data suggest that gene mutations and several other mechanisms result in NRF2 hyperactivation in human ESCC. As a consequence, NRF2high ESCC is more resistant to chemoradiotherapy and associated with poorer survival than NRF2low ESCC. Mechanistically, we believe NRF2, functioning as a transcription factor, causes an esophageal phenotype through regulation of gene transcription. We discuss metabolism, mitochondria, proteasomes, and several signaling pathways as downstream players that may contribute to an esophageal phenotype due to NRF2 hyperactivation. Finally, strategies are proposed to target the NRF2 signaling pathway for therapy of NRF2high ESCC.

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Citations

Nov 10, 2018·The Journal of Biological Chemistry·Junsheng FuXiaoxin Chen
Dec 19, 2019·Cellular Oncology (Dordrecht)·Ali Fatehi HassanabadJacques Raphael
Jul 10, 2019·Acta Biochimica Et Biophysica Sinica·Zhenghua ZhangMingfa Guo
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Jan 21, 2021·Journal of Cellular and Molecular Medicine·Yan-Qing LiJing Su
Jan 20, 2021·Cellular and Molecular Life Sciences : CMLS·Siyuan LuanYong Yuan
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Aug 7, 2021·Cellular Signalling·Chorlada PaiboonrungruangXiaoxin Chen
Jan 7, 2022·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·L K KadianS S Chauhan

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