University of Torino, Department of Oncology, Candiolo Cancer Institute-FPO, IRCCS, Strada Provinciale 142, 10060 Candiolo, Torino, Italy.
Department of Biomedical Sciences, University of Cagliari, Via Porcell 4, 09124 Cagliari, Italy.
Trends Mol Med. 2016 Jul;22(7):578-593. doi: 10.1016/j.molmed.2016.05.002. Epub 2016 Jun 2.
NRF2 has been traditionally considered as a tumor suppressor because its cytoprotective functions are deemed to be the main cellular defense mechanism against exogenous and endogenous insults, including xenobiotics and oxidative stress. However, several recent studies demonstrate that hyperactivation of the NRF2 pathway creates an environment that favors the survival of normal as well as malignant cells, protecting them against oxidative stress, chemotherapeutic agents, and radiotherapy. In a rapidly advancing field, this review summarizes some of the known mechanisms by which NRF2 can exert its oncogenic functions, and describes the current status of NRF2 inhibitors, providing a clear rationale for the consideration of NRF2 as a powerful putative therapeutic target in cancer treatment.
NRF2 传统上被认为是一种肿瘤抑制因子,因为其细胞保护功能被认为是细胞对外源和内源性损伤(包括异源物和氧化应激)的主要防御机制。然而,最近的几项研究表明,NRF2 通路的过度激活创造了一个有利于正常和恶性细胞存活的环境,使它们能够抵抗氧化应激、化疗药物和放射治疗。在这个快速发展的领域中,本文综述了 NRF2 发挥其致癌功能的一些已知机制,并描述了 NRF2 抑制剂的现状,为将 NRF2 作为癌症治疗中一种有前途的潜在治疗靶点提供了明确的依据。