Hasan Syed K, Jayakumar Sundarraj, Espina Barroso Eliezer, Jha Anup, Catalano Gianfranco, Sandur Santosh K, Noguera Nelida I
Hasan Lab, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai 410210, India.
Department of Life Sciences, Homi Bhabha National Institute, Mumbai 400094, India.
Cells. 2025 May 14;14(10):713. doi: 10.3390/cells14100713.
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that plays a central role in regulating cellular responses to oxidative stress. It governs the expression of a broad range of genes involved in antioxidant defense, detoxification, metabolism, and other cytoprotective pathways. In normal cells, the transient activation of Nrf2 serves as a protective mechanism to maintain redox homeostasis. However, the persistent or aberrant activation of Nrf2 in cancer cells has been implicated in tumor progression, metabolic reprogramming, and resistance to chemotherapy and radiotherapy. These dual roles underscore the complexity of Nrf2 signaling and its potential as a therapeutic target. A deeper understanding of Nrf2 regulation in both normal and malignant contexts is essential for the development of effective Nrf2-targeted therapies. This review provides a comprehensive overview of Nrf2 regulation and function, highlighting its unique features in cancer biology, particularly its role in metabolic adaptation and drug resistance. Special attention is given to the current knowledge of Nrf2's involvement in leukemia and emerging strategies for its therapeutic modulation.
核因子红细胞2相关因子2(Nrf2)是一种转录因子,在调节细胞对氧化应激的反应中起核心作用。它控制着广泛参与抗氧化防御、解毒、代谢和其他细胞保护途径的基因的表达。在正常细胞中,Nrf2的瞬时激活作为维持氧化还原稳态的一种保护机制。然而,癌细胞中Nrf2的持续或异常激活与肿瘤进展、代谢重编程以及对化疗和放疗的抗性有关。这些双重作用突显了Nrf2信号传导的复杂性及其作为治疗靶点的潜力。深入了解正常和恶性环境下的Nrf2调节对于开发有效的Nrf2靶向治疗至关重要。本综述全面概述了Nrf2的调节和功能,突出了其在癌症生物学中的独特特征,特别是其在代谢适应和耐药性中的作用。特别关注了目前关于Nrf2参与白血病的知识以及对其进行治疗性调节的新兴策略。