Glioblastomas: Hijacking Metabolism to Build a Flexible Shield for Therapy Resistance.
Glioblastomas: Hijacking Metabolism to Build a Flexible Shield for Therapy Resistance.
复制标题
胶质母细胞瘤：劫持新陈代谢以构建灵活的治疗抵抗盾。
DOI：
10.1089/ars.2022.0088
复制
发表时间：
2023
影响因子：
6.6
通讯作者：
Vlashi,Erina
中科院分区：
文献类型：
--
作者：
Bailleul,Justine;Vlashi,Erina
意义：胶质母细胞瘤（GBM）是最致命的肿瘤之一，尽管几乎只局限于大脑。这在很大程度上是由于耐药性。放疗和化疗可显著提高GBM患者的生存率，但GBM总是复发，中位总生存期仅为1年多。对治疗的这种顽固性抗性的提出的原因很多，包括肿瘤代谢，特别是肿瘤细胞按需重新配置代谢通量的能力（代谢可塑性）。了解硬连线，癌基因驱动的GBM的代谢趋势如何与灵活的，上下文诱导的代谢rewiring交叉，有望揭示新的方法来对抗therapeutic resistance.Recent Advances：个性化的基因组规模的代谢通量模型最近提供的证据表明，代谢的灵活性促进癌症的辐射抗性，并确定肿瘤氧化还原代谢作为抵抗放射治疗（RT）的主要预测因子。结果表明，抗辐射的肿瘤，包括GBM，重新路由代谢通量，以提高细胞的还原因子的水平，从而提高清除活性氧的RT和促进survival.Critical问题：从已发表的研究目前的知识体系强烈支持的概念，强大的代谢可塑性可以作为一个（灵活的）屏蔽标准GBM疗法的细胞毒性作用，从而驱动治疗抗性。这种代谢可塑性的关键驱动因素的有限的理解阻碍了合理设计的有效combinationtheraps.Future Directions：识别和靶向调节代谢可塑性，而不是特定的代谢途径，在结合标准的护理治疗有可能改善治疗结果GBM。抗氧化剂。Redox Signal.39，957-979.
Significance:Glioblastomas (GBMs) are among the most lethal tumors despite the almost exclusive localization to the brain. This is largely due to therapeutic resistance. Radiation and chemotherapy significantly increase the survival for GBM patients, however, GBMs always recur, and the median overall survival is just over a year. Proposed reasons for such intractable resistance to therapy are numerous and include tumor metabolism, in particular, the ability of tumor cells to reconfigure metabolic fluxes on demand (metabolic plasticity). Understanding how the hard-wired, oncogene-driven metabolic tendencies of GBMs intersect with flexible, context-induced metabolic rewiring promises to reveal novel approaches for combating therapy resistance.Recent Advances:Personalized genome-scale metabolic flux models have recently provided evidence that metabolic flexibility promotes radiation resistance in cancer and identified tumor redox metabolism as a major predictor for resistance to radiation therapy (RT). It was demonstrated that radioresistant tumors, including GBM, reroute metabolic fluxes to boost the levels of reducing factors of the cell, thus enhancing clearance of reactive oxygen species that are generated during RT and promoting survival.Critical Issues:The current body of knowledge from published studies strongly supports the notion that robust metabolic plasticity can act as a (flexible) shield against the cytotoxic effects of standard GBM therapies, thus driving therapy resistance. The limited understanding of the critical drivers of such metabolic plasticity hampers the rational design of effective combination therapies.Future Directions:Identifying and targeting regulators of metabolic plasticity, rather than specific metabolic pathways, in combination with standard-of-care treatments have the potential to improve therapeutic outcomes in GBM.Antioxid. Redox Signal.39, 957–979.