REVIEW article
Front. Oncol.
Sec. Gynecological Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1579135
This article is part of the Research TopicInnovative Theranostics: Image-Guided Nano-Radiopharmaceuticals in Cancer TreatmentView all 3 articles
The implication of aberrant NRF2 activation in management of female cancers
Provisionally accepted
Mankgopo Magdeline Kgatle1*
Saidon Mbambara1
Olalekan Fadebi1
Joseph Kabunda2Chimbabantu Kaoma1Thobeka Dlangalala1
Siphesihle Nxele3
Ndimo Modipane1
Thato Serite1
Kgomotso Mokoala1
Tivani Phosa Mashamba-Thompson3
Mike Sathekge1- 1Department of Nuclear Medicine, University of Pretoria, Nuclear Medicine Research Infrastructure, Pretoria, South Africa, Pretoria, South Africa
- 2Department of Nuclear Medicine, University of Pretoria,, Nuclear Medicine Research Infrastructure, Pretoria, South Africa, Pretoria, South Africa
- 3School of Health System and Public Health, Faculty of Health Sciences, University of Pretoria, Nuclear Medicine Research Infrastructure, Pretoria, South Africa, Pretoria, South Africa
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The overactivation of NRF2 (Nuclear factor erythroid 2-related factor 2) in female malignancies is an emerging field of study with significant implications for treatment efficacy. NRF2 plays a pivotal role in managing inflammation-induced oxidative stress, which is crucial components of the tumor microenvironment. Acting as a transcription factor and basic leucine zipper protein, it regulates the expression of various antioxidant genes that safeguard cells from oxidative stress and damage. While NRF2 activation is beneficial for the survival of normal cells, its overactivation in cancer cells can enhance tumor cell survival, proliferation, and resistance to treatments like chemotherapy and radiotherapy. This dual role positions NRF2 as a key therapeutic target; inhibiting it could potentially reduce cancer cells' resistance and slow down tumor progression. Understanding NRF2's transcriptional alterations and developing targeted therapies could improve cancer management, prognosis and treatment outcomes, making it a promising target for precision oncology. This review aims to provide a comprehensive overview of NRF2 activation in female malignancies, including cervical, endometrial, ovarian, vaginal, vulvar and, breast cancers, and its association with chemoresistance, highlighting challenges and opportunities for developing more effective cancer treatments.
Keywords: Nrf2 activation, Oxidative Stress, tumor progression, Therapyresistance, gynecological cancers, Targeted inhibitors, PET imaging, Personalizedtreatment
Received: 18 Feb 2025; Accepted: 13 Oct 2025.
Copyright: © 2025 Kgatle, Mbambara, Fadebi, Kabunda, Kaoma, Dlangalala, Nxele, Modipane, Serite, Mokoala, Mashamba-Thompson and Sathekge. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mankgopo Magdeline Kgatle, kgatle.mankgopo@gmail.com
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.