Emerging role of NRF2 in ROS-mediated tumor chemoresistance

Biomed Pharmacother. 2020 Nov:131:110676. doi: 10.1016/j.biopha.2020.110676. Epub 2020 Aug 25.

Abstract

Chemoresistance is a central cause for the tumor management failure. Cancer cells disrupt the redox homeostasis through reactive oxygen species (ROS) regulatory mechanisms, leading to tumor progression and chemoresistance. The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of neutralizing cellular ROS and restoring redox balance. Understanding the role of NRF2 in ROS-mediated chemoresistance can be helpful in the development of chemotherapy strategies with better efficiency. In this review, we sum up the roles of ROS in the development of chemoresistance to classical chemotherapy agents including cisplatin, 5-fluorouracil, gemcitabine, oxaliplatin, paclitaxel, and doxorubicin, and how to overcome ROS-mediated tumor chemoresistance by targeting NRF2. Finally, we propose that targeting NRF2 might be a promising strategy to resist ROS-driven chemoresistance and acquire better efficacy in cancer treatment.

Keywords: Chemoresistance; NRF2; Reactive oxygen species.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cell Death / drug effects
  • Cell Death / physiology
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / physiology*
  • Humans
  • NF-E2-Related Factor 2 / physiology*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Reactive Oxygen Species / metabolism*

Substances

  • Antineoplastic Agents
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Reactive Oxygen Species