Glioblastoma is an aggressive and heterogeneous tumor in which glioblastoma stem cells (GSCs) are at the apex of an entropic hierarchy and impart devastating therapy resistance. The high entropy of GSCs is driven by a permissive epigenetic landscape and a mutational landscape that revokes crucial cellular checkpoints. The GSC population encompasses a complex array of diverse microstates that are 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 therapy 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.

胶质母细胞瘤是一种侵袭性和异质性肿瘤，其中胶质母细胞瘤干细胞（GSC）位于熵层次结构的顶端，并赋予毁灭性的治疗抵抗力。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，这些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。