The Role of Nrf2 in Glioma: Therapeutic Targeting Strategies.

in Current cancer drug targets by Mohammad Sadra Harifi-Mood, Effat Alemzadeh, Danyal Barati, Amir Hossein Dehghani, Fatemeh Zahra Siroosi, Michael Aschner, Fariborz Samini, Saeed Samarghandian, Tahereh Farkhondeh

TLDR

  • This study investigates the role of Nrf2 in glioma development and treatment, demonstrating that Nrf2 inhibition increases chemotherapy efficacy and suggesting that Nrf2 targeting may be a promising new therapeutic approach.

Abstract

Cancer is one of the most challenging diseases to cure due to its complexity. Gli-oma, as a neuroepithelial cancer of the glial cells, is one of the rarest malignancies which has a low survival rate. The exact risk factors of glioma are still not clear, but allergy, ionizing radiation, and hereditary factors are reported to be associated with glioma. Nrf2 as an antiox-idant regulator has been reported to be highly expressed in malignances tissues like glioma. Nrf2 regulates the expression of various antioxidant and cytoprotective genes. In gliomas, Nrf2 activation helps tumor cells combat oxidative stress by enhancing the production of de-toxifying enzymes (e.g., glutathione peroxidase, NADPH quinone oxidoreductase). This al-lows glioma cells to survive and proliferate in toxic tumor microenvironments rich in reactive oxygen species (ROS). Although the role of Nrf2 in the apoptosis of cancerous glial cells is not clear yet, it has been shown that Nrf2 inhibition via different methods can increase the efficiency of the chemo-therapy agents to treat glioma. Elevated Nrf2 activity has been linked to drug resistance in gliomas. The activation of Nrf2 increases the expression of multidrug resistance-associated proteins (MRPs) and other detoxifying enzymes, which limit the effectiveness of chemother-apeutic agents like temozolomide (TMZ). Nrf2 inhibitors can suppress the signaling pathway of Nrf2 and decrease the expression of detoxifying enzymes like SOD, CAT, GPX, and GCL, which can increase the efficiency of chemotherapy agents. Using drugs that inhibit the Nrf2 expression in combination with classical chemotherapy agents can be a promising procedure to decrease chemoresistance and be effective in increasing the survival rate of patients with glioma. In this study, we focused on the association of glioma and Nrf2 expression and its targeting as a new therapeutic approach in glioma treatment.

Overview

  • The study explores the relationship between glioma, a rare and aggressive cancer, and Nrf2, an antioxidant regulator that plays a crucial role in cancer development and treatment.
  • The research focuses on the impact of Nrf2 expression on glioma progression and the potential of targeting Nrf2 as a new therapeutic approach.
  • The study aims to understand how Nrf2 contributes to glioma development and progression, and how its inhibition can enhance chemotherapy efficacy and patient survival rates.

Comparative Analysis & Findings

  • The study found that Nrf2 is highly expressed in glioma tissues and plays a key role in tumor growth and survival by inducing the expression of antioxidant and cytoprotective genes.
  • The research demonstrated that Nrf2 inhibition increased the efficiency of chemotherapy agents by suppressing the expression of detoxifying enzymes and multidrug resistance-associated proteins.
  • The study suggests that combining Nrf2 inhibitors with classical chemotherapy agents can be a promising approach to decrease chemoresistance and improve patient survival rates in glioma treatment.

Implications and Future Directions

  • The findings of this study have significant implications for the development of new therapeutic strategies for glioma treatment, including the use of Nrf2 inhibitors in combination with chemotherapy agents.
  • Future research should focus on identifying specific Nrf2 inhibitors and optimizing their dosing and administration schedule for glioma treatment.
  • Additionally, exploring the potential of Nrf2 targeting as a monotherapy or in combination with other therapies, such as immunotherapy or gene therapy, may provide further insights into its therapeutic potential.
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