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Targeted therapy of esophageal squamous cell carcinoma: the NRF2 signaling pathway as target
Author(s) -
Ma Shaohua,
Paiboonrungruan Chorlada,
Yan Tiansheng,
Williams Kevin P.,
Major M. Ben,
Chen Xiaoxin Luke
Publication year - 2018
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.13681
Subject(s) - hyperactivation , transcription factor , cancer research , phenotype , signal transduction , biology , esophagus , esophageal squamous cell carcinoma , gene , proteasome , bioinformatics , carcinoma , microbiology and biotechnology , genetics , anatomy
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, NRF2 high ESCC is more resistant to chemoradiotherapy and associated with poorer survival than NRF2 low 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 NRF2 high ESCC.