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Ferroptosis at the crossroads of cancer-acquired drug resistance and immune evasion.
Nature Reviews Cancer ( IF 72.5 ) Pub Date : 2019-07-01 , DOI: 10.1038/s41568-019-0149-1 José Pedro Friedmann Angeli 1 , Dmitri V Krysko 2, 3 , Marcus Conrad 4
Nature Reviews Cancer ( IF 72.5 ) Pub Date : 2019-07-01 , DOI: 10.1038/s41568-019-0149-1 José Pedro Friedmann Angeli 1 , Dmitri V Krysko 2, 3 , Marcus Conrad 4
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Ferroptosis is a recently recognized cell death modality that is morphologically, biochemically and genetically distinct from other forms of cell death and that has emerged to play an important role in cancer biology. Recent discoveries have highlighted the metabolic plasticity of cancer cells and have provided intriguing insights into how metabolic rewiring is a critical event for the persistence, dedifferentiation and expansion of cancer cells. In some cases, this metabolic reprogramming has been linked to an acquired sensitivity to ferroptosis, thus opening up new opportunities to treat therapy-insensitive tumours. However, it is not yet clear what metabolic determinants are critical for therapeutic resistance and evasion of immune surveillance. Therefore, a better understanding of the processes that regulate ferroptosis sensitivity should ultimately aid in the discovery of novel therapeutic strategies to improve cancer treatment. In this Perspectives article, we provide an overview of the known mechanisms that regulate sensitivity to ferroptosis in cancer cells and how the modulation of metabolic pathways controlling ferroptosis might reshape the tumour niche, leading to an immunosuppressive microenvironment that promotes tumour growth and progression.
中文翻译：
处于癌症获得性耐药性和免疫逃避十字路口的铁死亡。
铁死亡是最近公认的细胞死亡方式，在形态学、生物化学和遗传上与其他形式的细胞死亡不同，并且已在癌症生物学中发挥重要作用。最近的发现突出了癌细胞的代谢可塑性，并提供了关于代谢重新布线如何成为癌细胞持续、去分化和扩增的关键事件的有趣见解。在某些情况下，这种代谢重编程与获得性对铁死亡的敏感性有关，从而为治疗对治疗不敏感的肿瘤开辟了新的机会。然而，目前尚不清楚哪些代谢决定因素对治疗耐药性和逃避免疫监视至关重要。所以，更好地理解调节铁死亡敏感性的过程最终将有助于发现新的治疗策略以改善癌症治疗。在这篇 Perspectives 文章中，我们概述了调节癌细胞对铁死亡敏感性的已知机制，以及调节控制铁死亡的代谢途径如何重塑肿瘤生态位，从而形成促进肿瘤生长和进展的免疫抑制微环境。
更新日期：2019-05-20
中文翻译：
处于癌症获得性耐药性和免疫逃避十字路口的铁死亡。
铁死亡是最近公认的细胞死亡方式，在形态学、生物化学和遗传上与其他形式的细胞死亡不同，并且已在癌症生物学中发挥重要作用。最近的发现突出了癌细胞的代谢可塑性，并提供了关于代谢重新布线如何成为癌细胞持续、去分化和扩增的关键事件的有趣见解。在某些情况下，这种代谢重编程与获得性对铁死亡的敏感性有关，从而为治疗对治疗不敏感的肿瘤开辟了新的机会。然而，目前尚不清楚哪些代谢决定因素对治疗耐药性和逃避免疫监视至关重要。所以，更好地理解调节铁死亡敏感性的过程最终将有助于发现新的治疗策略以改善癌症治疗。在这篇 Perspectives 文章中，我们概述了调节癌细胞对铁死亡敏感性的已知机制，以及调节控制铁死亡的代谢途径如何重塑肿瘤生态位，从而形成促进肿瘤生长和进展的免疫抑制微环境。
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