Glioblastoma (GBM) is regarded as the most common primary intracranial neoplasm. Despite standard treatment with tumor resection and radiochemotherapy, the outcome remains gloomy. It is evident that a combination of oncogenic gain of function and tumor‐suppressive loss of function has been attributed to glioma initiation and progression. The ubiquitin–proteasome system is a well‐orchestrated system that controls the fate of most proteins by striking a dynamic balance between ubiquitination and deubiquitination of substrates, having a profound influence on the modulation of oncoproteins, tumor suppressors, and cellular signaling pathways. In recent years, deubiquitinating enzymes (DUBs) have emerged as potential anti‐cancer targets due to their targeting several key proteins involved in the regulation of tumorigenesis, apoptosis, senescence, and autophagy. This review attempts to summarize recent studies of GBM‐associated DUBs, their roles in various cellular processes, and discuss the relation between DUBs deregulation and gliomagenesis, especially how DUBs regulate glioma stem cells pluripotency, microenvironment, and resistance of radiation and chemotherapy through core stem‐cell transcriptional factors. We also review recent achievements and progress in the development of potent and selective reversible inhibitors of DUBs, and attempted to find a potential GBM treatment by DUBs intervention.

中文翻译：

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靶向胶质母细胞瘤中的去泛素化酶：期望和挑战

胶质母细胞瘤（GBM）被认为是最常见的原发性颅内肿瘤。尽管采用了肿瘤切除术和放射化学疗法的标准治疗方法，结果仍然令人沮丧。显然，致癌性功能增强和肿瘤抑制性功能丧失的组合被归因于神经胶质瘤的发生和发展。泛素-蛋白酶体系统是精心设计的系统，它通过在底物的泛素化和去泛素化之间实现动态平衡来控制大多数蛋白质的命运，对癌蛋白，肿瘤抑制因子和细胞信号通路的调节产生深远影响。近年来，去泛素化酶（DUBs）已成为潜在的抗癌靶标，因为它们靶向调控肿瘤发生，凋亡，衰老，和自噬。这篇综述试图总结与GBM相关的DUB的最新研究及其在各种细胞过程中的作用，并讨论DUB解除调节与神经胶质瘤形成之间的关系，尤其是DUB如何调节神经胶质瘤干细胞的多能性，微环境以及通过核心干对放射线和化疗的抵抗细胞转录因子。我们还回顾了有效和选择性可逆性DUBs抑制剂开发的最新成就和进展，并尝试通过DUBs干预寻找潜在的GBM治疗方法。核心干细胞转录因子对放射线和化学疗法的抵抗力。我们还回顾了有效和选择性可逆性DUBs抑制剂开发的最新成就和进展，并尝试通过DUBs干预寻找潜在的GBM治疗方法。核心干细胞转录因子对放射线和化学疗法的抵抗力。我们还回顾了有效和选择性可逆性DUBs抑制剂开发的最新成就和进展，并尝试通过DUBs干预寻找潜在的GBM治疗方法。