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适应性变化可使铁死亡成为治疗脑胶质瘤的新靶点。

Adaptive Changes Allow Targeting of Ferroptosis for Glioma Treatment.

机构信息

Department of Neurosurgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, China.

Department of Neurology, China-Japan Union Hospital, Jilin University, Changchun, Jilin, China.

出版信息

Cell Mol Neurobiol. 2022 Oct;42(7):2055-2074. doi: 10.1007/s10571-021-01092-5. Epub 2021 Apr 24.

DOI:10.1007/s10571-021-01092-5
PMID:33893939
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11421619/
Abstract

Ferroptosis is a type of regulated cell death that plays an essential role in various brain diseases, including cranial trauma, neuronal diseases, and brain tumors. It has been reported that cancer cells rely on their robust antioxidant capacity to escape ferroptosis. Therefore, ferroptosis exploitation could be an effective strategy to prevent tumor proliferation and invasion. Glioma is a common malignant craniocerebral tumor exhibiting complicated drug resistance and survival mechanisms, resulting in a high mortality rate and short survival time. Recent studies have determined that metabolic alterations in glioma offer exploitable therapeutic targets. These metabolic alterations allow targeted therapy to achieve some initial efficacy but have failed to inhibit glioma growth, invasion, and drug resistance effectively. It has been proposed that the reason for the high malignancy and drug resistance observed with glioma is that these tumors can effectively evade ferroptosis. Ferroptosis-inducing drugs were found to exert a positive effect by targeting this particular characteristic of glioma cells. Moreover, gliomas develop enhanced drug resistance through anti-ferroptosis mechanisms. In this study, we provided an overview of the mechanisms by which glioma aggressiveness and drug resistance are mediated by the evasion of ferroptosis. This information might provide new targets for glioma therapy as well as new insights and ideas for future research.

摘要

铁死亡是一种调节性细胞死亡,在多种脑疾病中发挥着重要作用,包括颅脑创伤、神经元疾病和脑肿瘤。据报道,癌细胞依赖其强大的抗氧化能力来逃避铁死亡。因此,铁死亡的利用可能是预防肿瘤增殖和侵袭的有效策略。脑胶质瘤是一种常见的恶性颅脑肿瘤,具有复杂的耐药和生存机制,导致死亡率高、生存时间短。最近的研究确定,脑胶质瘤的代谢改变提供了可利用的治疗靶点。这些代谢改变允许靶向治疗达到一定的初步疗效,但未能有效抑制脑胶质瘤的生长、侵袭和耐药性。有人提出,脑胶质瘤之所以具有高恶性和耐药性,是因为这些肿瘤可以有效地逃避铁死亡。通过针对脑胶质瘤细胞的这一特定特征,铁死亡诱导药物被发现具有积极的效果。此外,脑胶质瘤通过抗铁死亡机制发展出增强的耐药性。在本研究中,我们综述了脑胶质瘤通过逃避铁死亡来介导侵袭性和耐药性的机制。这些信息可能为脑胶质瘤治疗提供新的靶点,并为未来的研究提供新的见解和思路。

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