TY - JOUR
T1 - Targeted therapy of esophageal squamous cell carcinoma
T2 - the NRF2 signaling pathway as target
AU - Ma, Shaohua
AU - Paiboonrungruan, Chorlada
AU - Yan, Tiansheng
AU - Williams, Kevin P.
AU - Major, M. Ben
AU - Chen, Xiaoxin Luke
N1 - Funding Information:
The authors are supported by a Faculty Development Fund from Peking University Third Hospital, NIH/NCI U54 CA156735, and NIH/NIMHD U54 MD012392.
Publisher Copyright:
© 2018, John Wiley and Sons Inc. All rights reserved.
PY - 2018/12
Y1 - 2018/12
N2 - 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 hyperacti-vation 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.
AB - 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 hyperacti-vation 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.
KW - KEAP1
KW - NRF2
KW - esophageal squamous cell carcinoma
KW - targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85046777354&partnerID=8YFLogxK
U2 - 10.1111/nyas.13681
DO - 10.1111/nyas.13681
M3 - Article
C2 - 29752726
AN - SCOPUS:85046777354
SN - 0077-8923
VL - 1434
SP - 164
EP - 172
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
IS - 1
ER -