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Role of NRF2 in Lung Cancer

Miriam Sánchez-Ortega1, Ana Clara Carrera1, Antonio Garrido1

  • 1Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, Spain.

Cells
|August 27, 2021
PubMed

Insights

The NRF2-KEAP1 pathway protects cells from stress but can drive lung cancer progression and chemotherapy resistance. Targeting NRF2 offers potential therapeutic strategies for these tumors.

Area of Science:

  • Molecular Biology
  • Cellular Stress Response
  • Oncology

Background:

  • The NRF2 transcription factor regulates cellular defense against oxidative stress.
  • KEAP1 protein controls NRF2 stability, targeting it for degradation under normal conditions.
  • Initially viewed as anti-cancer, NRF2 now shows pro-tumoral roles in metastasis and chemoresistance.

Purpose of the Study:

  • To review the molecular mechanisms of the NRF2/KEAP1 pathway in physiology.
  • To summarize NRF2/KEAP1's role in lung cancer development and progression.
  • To discuss therapeutic strategies targeting NRF2 in lung cancer.

Main Methods:

  • Literature review of NRF2/KEAP1 signaling.
  • Analysis of NRF2 activation mechanisms in cancer.
  • Summary of therapeutic interventions targeting NRF2.

Main Results:

  • NRF2 activation is frequent in lung cancers, promoting malignant phenotypes.
  • The dual role of NRF2 (cytoprotective vs. pro-tumoral) creates controversy in cancer research.
  • NRF2 contributes to lung cancer metastasis and resistance to treatments.

Conclusions:

  • The NRF2/KEAP1 pathway has complex, context-dependent roles in lung cancer.
  • Understanding NRF2 activation is crucial for developing effective lung cancer therapies.
  • Targeting NRF2 represents a promising therapeutic avenue for lung cancer treatment.
Keywords:
NRF2 activationNSCLCtherapeutic strategies

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