The Nrf2 (nuclear factor erythroid 2 [NF-E2]-related factor 2 [Nrf2])-Keap1 (Kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein 1) signaling pathway is one of the most important cell defense and survival pathways. Nrf2 can protect cells and tissues from a variety of toxicants and carcinogens by increasing the expression of a number of cytoprotective genes. As a result, several Nrf2 activators are currently being tested as chemopreventive compounds in clinical trials. Just as Nrf2 protects normal cells, studies have shown that Nrf2 may also protect cancer cells from chemotherapeutic agents and facilitate cancer progression. Nrf2 is aberrantly accumulated in many types of cancer, and its expression is associated with a poor prognosis in patients. In addition, Nrf2 expression is induced during the course of drug resistance. Collectively, these studies suggest that Nrf2 contributes to both intrinsic and acquired chemoresistance. This discovery has opened up a broad spectrum of research geared toward a better understanding of the role of Nrf2 in cancer. This review provides an overview of (1) the Nrf2-Keap1 signaling pathway, (2) the dual role of Nrf2 in cancer, (3) the molecular basis of Nrf2 activation in cancer cells, and (4) the challenges in the development of Nrf2-based drugs for chemoprevention and chemotherapy.

译文

:Nrf2(核因子红系2 [NF-E2]-相关因子2 [Nrf2])-Keap1(与Kelch样红系细胞衍生的蛋白具有CNC同源性[ECH]相关蛋白1)信号通路是最重要的信号途径之一重要的细胞防御和生存途径。 Nrf2可以通过增加许多细胞保护性基因的表达来保护细胞和组织免受多种毒物和致癌物的侵害。结果,目前正在临床试验中将几种Nrf2激活剂作为化学预防化合物进行测试。正如Nrf2保护正常细胞一样,研究表明Nrf2也可以保护癌细胞免受化学治疗剂的侵害并促进癌症的进展。 Nrf2在许多类型的癌症中异常积累,其表达与患者预后不良有关。另外,在耐药过程中诱导了Nrf2表达。总体而言,这些研究表明Nrf2有助于内在和获得性化学抗性。这项发现开辟了广泛的研究,旨在更好地了解Nrf2在癌症中的作用。这篇综述概述了(1)Nrf2-Keap1信号传导途径,(2)Nrf2在癌症中的双重作用,(3)Nrf2在癌细胞中激活的分子基础,以及(4)肝癌发展中的挑战基于Nrf2的化学预防和化学治疗药物。

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