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

Shaohua Ma, Chorlada Paiboonrungruan, Tiansheng Yan, Kevin P. Williams, M. Ben Major, Xiaoxin Luke Chen

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


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.

Original languageEnglish
Pages (from-to)164-172
Number of pages9
JournalAnnals of the New York Academy of Sciences
Issue number1
StatePublished - Dec 2018


  • KEAP1
  • NRF2
  • esophageal squamous cell carcinoma
  • targeted therapy


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