Xia Yangchen, Xu Ziyang, Yuan Xun, Chu Qian
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Invest New Drugs. 2025 Sep 5. doi: 10.1007/s10637-025-01578-9.
The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is the first-line regulator of a plethora of cytoprotective pathways, such as inflammation, redox metabolism, and proteostasis. Besides its protective role in oxidative stress, several recent advances suggested that the Nrf2 pathway is extensively involved in cancer pathogenesis and confers a survival advantage and malignant transformation. Therefore, pharmacological inhibition of Nrf2 is a potential therapeutic approach for cancer that is related to oxidative stress and inflammation. In this review, we first describe the molecular regulatory mechanisms of Nrf2 and its biological function in cancer. Then, we discuss the recent progress of blocking Nrf2 activity, comprising novel chemical molecules, and the advance in preclinical or clinical trials in cancer therapy.
转录因子核因子红细胞2相关因子2（Nrf2）是众多细胞保护途径的一线调节因子，如炎症、氧化还原代谢和蛋白质稳态。除了其在氧化应激中的保护作用外，最近的一些进展表明，Nrf2途径广泛参与癌症发病机制，并赋予生存优势和恶性转化能力。因此，对Nrf2进行药理学抑制是一种针对与氧化应激和炎症相关癌症的潜在治疗方法。在本综述中，我们首先描述Nrf2的分子调控机制及其在癌症中的生物学功能。然后，我们讨论阻断Nrf2活性的最新进展，包括新型化学分子，以及癌症治疗临床前或临床试验的进展。
