Glioblastoma Stem Cells: Driving Resilience through Chaos.

Glioblastoma Stem Cells: Driving Resilience through Chaos.
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DOI:
10.1016/j.trecan.2020.01.009
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发表时间:
2020-03
期刊:
影响因子:
18.4
通讯作者:
Rich JN
Rich JN
中科院分区:
医学1区
文献类型:
--
作者:
Prager BC;Bhargava S;Mahadev V;Hubert CG;Rich JN

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胶质母细胞瘤是一种侵袭性和异质性肿瘤,胶质母细胞瘤干细胞(GSC)位于熵层次结构的顶端,具有毁灭性的治疗耐药性。 GSC 的高熵是由宽松的表观遗传景观和撤销关键细胞检查点的突变景观驱动的。 GSC 群体包含一系列复杂的不同微观状态,由各种吸引子定义和维持,包括复杂的肿瘤生态系统和治疗干预。持续的动态转录波动会产生高度适应性和异质性的实体,为逃避治疗和生存做好准备。在随机波动的肿瘤网络背景下分析 GSC 动态的转录、表观遗传和代谢景观将为靶向胶质母细胞瘤中 GSC 耐药群体提供新策略。
Glioblastoma is an aggressive and heterogeneous tumor, with glioblastoma stem cells (GSCs) at the apex of an entropic hierarchy, imparting devastating therapeutic resistance. The high entropy of GSCs is driven by a permissive epigenetic landscape and a mutational landscape that revokes critical cellular checkpoints. The GSC population encompasses a complex array of diverse microstates, defined and maintained by a wide variety of attractors including the complex tumor ecosystem and therapeutic intervention. Constant dynamic transcriptional fluctuations result in a highly adaptable and heterogeneous entity, primed for therapeutic evasion and survival. Analyzing the transcriptional, epigenetic and metabolic landscapes of GSC dynamics in the context of a stochastically fluctuating tumor network will provide novel strategies to target resistant populations of GSCs in glioblastoma.
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