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Targeting the NF-E2-related factor 2 pathway: a novel strategy for glioblastoma (review)
Jianhong Zhu1, Handong Wang1, Youwu Fan1
1Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.
Abstract:
Glioblastoma is the most common and malignant subtype among all brain tumors. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an essential component of cellular defense against a variety of endogenous and exogenous stresses. A marked increase in research over the past few decades focusing on Nrf2 and its role in regulating glioblastoma has revealed the potential value of Nrf2 in the treatment of glioblastoma. In the present review, we discuss a novel framework of Nrf2 in the regulation of glioblastoma and the mechanisms regarding the downregulation of Nrf2 in treating glioblastoma. The candidate mechanisms include direct and indirect means. Direct mechanisms target tumor molecular pathways in order to overcome resistance to chemotherapy and radiotherapy, to inhibit proliferation, to block invasion and migration, to induce apoptosis, to promote differentiation, to enhance autophagy and to target glioblastoma stem cells. Indirect mechanisms target the reaction between glioblastoma cells and the surrounding microenvironment. Overall, the value of the Nrf2 pathway in glioblastoma provides a promising opportunity for new approaches by which to treat glioblastoma.
Insights
Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a key role in glioblastoma. Targeting Nrf2 offers new therapeutic strategies for this aggressive brain cancer.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Research
Background:
- Glioblastoma is the most aggressive primary brain tumor.
- Nuclear factor erythroid 2-related factor 2 (Nrf2) is crucial for cellular defense against stress.
- Nrf2's role in glioblastoma is increasingly recognized for therapeutic potential.
Purpose of the Study:
- To review the novel framework of Nrf2 in glioblastoma regulation.
- To discuss mechanisms for Nrf2 downregulation in glioblastoma treatment.
- To explore direct and indirect therapeutic strategies targeting Nrf2.
Main Methods:
- Literature review of Nrf2's role in glioblastoma.
- Analysis of direct mechanisms targeting tumor pathways.
- Examination of indirect mechanisms involving the tumor microenvironment.
Main Results:
- Nrf2 influences glioblastoma proliferation, invasion, migration, apoptosis, and differentiation.
- Direct Nrf2 targeting can overcome chemo- and radioresistance.
- Indirect targeting modulates glioblastoma-microenvironment interactions.
Conclusions:
- The Nrf2 pathway presents a promising target for novel glioblastoma treatments.
- Understanding Nrf2 regulation is key to developing effective therapeutic approaches.
- Targeting Nrf2 offers potential for improved glioblastoma management.
