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Emerging role of NRF2 in ROS-mediated tumor chemoresistance

Danfeng Xue1, Xiongming Zhou1, Jiaxuan Qiu1

  • 1Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|August 29, 2020
PubMed

Insights

Targeting the NRF2 pathway can overcome chemoresistance in cancer. This approach addresses how cancer cells use reactive oxygen species (ROS) to resist treatment, offering a promising strategy for improved chemotherapy efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Chemoresistance is a major obstacle in cancer treatment, often driven by cancer cells disrupting cellular redox homeostasis.
  • Reactive oxygen species (ROS) play a critical role in tumor progression and the development of resistance to chemotherapy.
  • The transcription factor NRF2 (nuclear factor erythroid 2-related factor 2) is a key regulator of cellular antioxidant responses and redox balance.

Purpose of the Study:

  • To review the multifaceted roles of ROS in mediating chemoresistance to common chemotherapeutic agents.
  • To explore strategies for overcoming ROS-induced chemoresistance by targeting the NRF2 pathway.
  • To evaluate the potential of NRF2 as a therapeutic target for enhancing chemotherapy effectiveness.

Main Methods:

  • Literature review summarizing existing research on ROS, NRF2, and chemoresistance.
  • Analysis of the mechanisms by which ROS contribute to resistance against drugs like cisplatin, 5-fluorouracil, gemcitabine, oxaliplatin, paclitaxel, and doxorubicin.
  • Synthesis of findings to propose therapeutic strategies focused on modulating NRF2 activity.

Main Results:

  • ROS accumulation and altered redox balance are consistently linked to chemoresistance across various cancer types and treatments.
  • NRF2 activation promotes cancer cell survival under oxidative stress, contributing to treatment failure.
  • Targeting NRF2 presents a viable approach to sensitize tumors to chemotherapy by disrupting ROS-mediated resistance mechanisms.

Conclusions:

  • Modulating the NRF2 pathway holds significant promise for overcoming ROS-driven chemoresistance.
  • Targeting NRF2 could lead to more effective cancer chemotherapy strategies and improved patient outcomes.
  • Further research into NRF2-targeted therapies is warranted for clinical application in cancer treatment.
Keywords:
ChemoresistanceNRF2Reactive oxygen species

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