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

24 Scopus citations

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.

Original languageEnglish
JournalAnnals of the New York Academy of Sciences
DOIs
StateAccepted/In press - 2018

Keywords

  • Esophageal squamous cell carcinoma
  • KEAP1
  • NRF2
  • Targeted therapy

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