Related Experiment Video

Updated: Jun 4, 2025

Quantitative Analysis of Autophagy using Advanced 3D Fluorescence Microscopy
09:59

Quantitative Analysis of Autophagy using Advanced 3D Fluorescence Microscopy

Published on: May 3, 2013

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NRF-mediated autophagy and UPR: Exploring new avenues to overcome cancer chemo-resistance

Sanaz Dastghaib1, Sayed Mohammad Shafiee2, Fatemeh Ramezani3

  • 1Endocrinology and Metabolism Research Center, Shiraz University of Medical Sciences, 7193635899, Shiraz, Iran.

European Journal of Pharmacology
|December 20, 2024
PubMed

Insights

Nuclear factor erythroid 2-related factor 2 (NRF2) has a dual role in cancer, protecting normal cells but aiding tumor survival and chemoresistance. Targeting NRF signaling pathways may overcome drug resistance in cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • Chemoresistance is a major challenge in cancer treatment.
  • Nuclear factor erythroid 2-related factor 1 (NRF1) and NRF2 regulate redox homeostasis and cellular responses to oxidative stress.
  • NRF2 exhibits a dual role, protecting normal cells while promoting tumor survival and chemoresistance.

Purpose of the Study:

  • To investigate the dualistic role of NRF2 in cancer.
  • To explore the interplay between the PERK/NRF signaling pathway, ER stress, autophagy, and the unfolded protein response in chemoresistance.
  • To identify NRF signaling pathways as potential therapeutic targets for overcoming chemoresistance.

Main Methods:

  • Investigated the molecular mechanisms underlying NRF2's role in chemoresistance.
  • Examined the interplay of PERK/NRF signaling, ER stress, autophagy, and unfolded protein response.
  • Analyzed the impact of targeting NRF pathways on chemoresistance.

Main Results:

  • NRF2 paradoxically supports tumor survival and drug resistance in cancer cells.
  • The PERK/NRF pathway, ER stress, autophagy, and unfolded protein response are implicated in chemoresistance.
  • Targeting NRF signaling pathways shows potential for overcoming chemoresistance.

Conclusions:

  • NRF2's dual role necessitates a nuanced approach to redox regulation in cancer therapy.
  • Targeting NRF signaling pathways offers a promising strategy to enhance existing cancer treatments.
  • This research provides a molecular basis for developing NRF-targeted therapies against resistant tumors.
Keywords:
AutophagyDrug resistanceNF-E2-related factor 2Reactive oxygen speciesUnfolded protein response

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