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Development of Compendium for Esophageal Squamous Cell Carcinoma
03:36

Development of Compendium for Esophageal Squamous Cell Carcinoma

Published on: April 12, 2024

856

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

Shaohua Ma1,2, Chorlada Paiboonrungruan2, Tiansheng Yan1

  • 1Department of Thoracic Surgery, Peking University Third Hospital, Beijing, China.

Annals of the New York Academy of Sciences
|May 13, 2018
PubMed

Insights

The nuclear factor erythroid-derived 2-like 2 (NRF2) pathway is hyperactivated in esophageal squamous cell carcinoma (ESCC), leading to treatment resistance and poor survival. Targeting NRF2 offers a potential therapeutic strategy for ESCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Esophageal squamous cell carcinoma (ESCC) is a significant global health challenge.
  • The nuclear factor erythroid-derived 2-like 2 (NRF2) signaling pathway plays a critical role in cellular defense mechanisms.
  • Dysregulation of NRF2 is implicated in various cancers, including ESCC.

Purpose of the Study:

  • To review the current understanding of NRF2 pathway functions in the esophagus.
  • To explore the mechanisms of NRF2 hyperactivation in human ESCC.
  • To discuss the implications of NRF2 dysregulation for ESCC prognosis and treatment.

Main Methods:

  • Review of genomic data and existing literature on NRF2 in ESCC.
  • Analysis of NRF2's role as a transcription factor.
  • Discussion of downstream molecular pathways affected by NRF2 hyperactivation.

Main Results:

  • Genomic alterations frequently lead to NRF2 hyperactivation in ESCC.
  • NRF2-high ESCC exhibits increased resistance to chemoradiotherapy.
  • NRF2-high ESCC is associated with poorer patient survival outcomes.

Conclusions:

  • NRF2 hyperactivation drives an esophageal cancer phenotype through transcriptional regulation.
  • Metabolism, mitochondria, and proteasome function are key downstream effectors of NRF2 in ESCC.
  • Targeting the NRF2 pathway presents a promising therapeutic avenue for NRF2-high ESCC.
Keywords:
KEAP1NRF2esophageal squamous cell carcinomatargeted therapy

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