NRF2 addiction in cancer cells.
NRF2 addiction in cancer cells.
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DOI：
10.1111/cas.13537
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发表时间：
2018-04
期刊：
影响因子：
5.7
通讯作者：
Motohashi H
中科院分区：
文献类型：
--
作者：
Kitamura H;Motohashi H
Kelch 样 ECH 相关蛋白 1/核因子红细胞衍生 2 样 2 (KEAP1-NRF2) 系统是对抗氧化和亲电应激的关键防御机制。虽然应激反应中短暂的 NRF2 激活对健康有益，但癌细胞中持续的 NRF2 激活会对癌症宿主产生有害影响，因为癌细胞会产生治疗耐药性和侵袭性致瘤活性。由于NRF2增加癌细胞的抗氧化和解毒能力，持续高水平的NRF2活性可增强癌细胞的治疗抵抗力。 NRF2 还驱动代谢重编程，以建立有利于细胞增殖的细胞代谢过程，并与其他致癌途径合作。由于这些优势，NRF2持续激活的癌细胞常常会产生“NRF2成瘾”并表现出恶性表型，导致癌症患者预后不良。 NRF2 的抑制是治疗 NRF2 成瘾性癌症的一种有前途的治疗方法，并且 NRF2 抑制剂正在积极开发中。然而，考虑到 NRF2 在细胞保护中的核心作用，全身性 NRF2 抑制剂可能会对癌症宿主产生不良影响。为了避免这些副作用，除了 NRF2 之外，人们还积极探索针对 NRF2 成瘾癌症的新治疗靶点。这篇综述介绍了最近描述 NRF2 成瘾癌症的发展和特征及其潜在治疗靶点的研究。还讨论了 NRF2 成瘾癌症的诊断和治疗干预措施的预期进展。
The Kelch‐like ECH‐associated protein 1/nuclear factor erythroid‐derived 2‐like 2 (KEAP1‐NRF2) system is a pivotal defense mechanism against oxidative and electrophilic stress. Although transient NRF2 activation in response to stress is beneficial for health, persistent NRF2 activation in cancer cells has deleterious effects on cancer‐bearing hosts by conferring therapeutic resistance and aggressive tumorigenic activity on cancer cells. Because NRF2 increases the antioxidant and detoxification capability of cancer cells, persistently high levels of NRF2 activity enhance therapeutic resistance of cancer cells. NRF2 also drives metabolic reprogramming to establish cellular metabolic processes that are advantageous for cell proliferation in cooperation with other oncogenic pathways. As a result of these advantages, cancer cells with persistent activation of NRF2 often develop “NRF2 addiction” and show malignant phenotypes leading to poor prognoses in cancer patients. Inhibition of NRF2 is a promising therapeutic approach for NRF2‐addicted cancers and NRF2 inhibitors are being actively developed. However, giving systemic NRF2 inhibitors might have undesirable effects on cancer‐bearing hosts, considering the central roles of NRF2 in cytoprotection. To avoid these side‐effects, new therapeutic targets besides NRF2 for NRF2‐addicted cancers have been actively explored. This review introduces recent studies describing the development and characterization of NRF2‐addicted cancers, as well as their potential therapeutic targets. Expected advances in diagnostic and therapeutic interventions for NRF2‐addicted cancers are also discussed.
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影响因子：
--
作者：
Hu, Xiu-Feng;Yao, Jun;Feng, Xiao-Shan
通讯作者：
Feng, Xiao-Shan
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DOI：
10.1158/1078-0432.ccr-17-1841
发表时间：
2018-01-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
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作者：
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影响因子：
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通讯作者：
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影响因子：
64.5
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通讯作者：
Tuveson DA
影响因子：
8
作者：
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通讯作者：
Hayes, J. D.