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The implication of aberrant NRF2 activation in management of female cancers

Mankgopo Kgatle1,2,3, Saidon Mbambara1,2,4, Olalekan Fadebi1,2

  • 1Nuclear Medicine Research Infrastructure, Department of Basic and Translational Research, Pretoria, South Africa.

Frontiers in Oncology
|December 3, 2025
PubMed

Insights

Overactivation of Nuclear factor erythroid 2-related factor 2 (NRF2) promotes cancer cell survival and treatment resistance in female malignancies. Targeting NRF2 offers a promising strategy for improving precision oncology outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor regulating antioxidant genes.
  • NRF2 plays a dual role in cancer: tumor suppressor in normal cells and oncogene in established tumors.
  • NRF2 overactivation in the tumor microenvironment contributes to inflammation-induced oxidative stress and cancer progression.

Purpose of the Study:

  • To provide a comprehensive overview of NRF2 activation in female malignancies.
  • To explore the association between NRF2 and chemoresistance in these cancers.
  • To highlight challenges and opportunities for developing targeted NRF2 therapies.

Main Methods:

  • Literature review of NRF2's role in cervical, endometrial, ovarian, vaginal, vulvar, and breast cancers.
  • Analysis of NRF2's transcriptional alterations and its impact on treatment efficacy.
  • Examination of NRF2's context-dependent functions in carcinogenesis and tumor progression.

Main Results:

  • NRF2 overactivation enhances tumor cell survival, proliferation, and treatment resistance.
  • Persistent NRF2 activation acts as an oncogene in established tumors.
  • NRF2's role varies depending on its activation status and cellular context.

Conclusions:

  • Understanding NRF2's role is crucial for improving cancer management and prognosis.
  • Targeted therapies against NRF2 present a promising avenue for precision oncology.
  • Further research into NRF2 alterations can lead to more effective cancer treatments.
Keywords:
NRF2 activationPET imaginggynecological cancersoxidative stresspersonalized treatmenttargeted inhibitorstherapy resistancetumor progression

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