Luo Maowen, Luan Xingzhao, Yang Chaoge, Chen Xiaofan, Yuan Suxin, Cao Youlin, Zhang Jing, Xie Jiaying, Luo Qinglian, Chen Ligang, Li Shenjie, Xiang Wei, Zhou Jie
Department of Neurosurgery, the Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, China.
School of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan, China.
Front Oncol. 2024 Aug 9;14:1397863. doi: 10.3389/fonc.2024.1397863. eCollection 2024.
Gliomas are primary tumors that originate in the central nervous system. The conventional treatment options for gliomas typically encompass surgical resection and temozolomide (TMZ) chemotherapy. However, despite aggressive interventions, the median survival for glioma patients is merely about 14.6 months. Consequently, there is an urgent necessity to explore innovative therapeutic strategies for treating glioma. The foundational study of regulated cell death (RCD) can be traced back to Karl Vogt's seminal observations of cellular demise in toads, which were documented in 1842. In the past decade, the Nomenclature Committee on Cell Death (NCCD) has systematically classified and delineated various forms and mechanisms of cell death, synthesizing morphological, biochemical, and functional characteristics. Cell death primarily manifests in two forms: accidental cell death (ACD), which is caused by external factors such as physical, chemical, or mechanical disruptions; and RCD, a gene-directed intrinsic process that coordinates an orderly cellular demise in response to both physiological and pathological cues. Advancements in our understanding of RCD have shed light on the manipulation of cell death modulation - either through induction or suppression - as a potentially groundbreaking approach in oncology, holding significant promise. However, obstacles persist at the interface of research and clinical application, with significant impediments encountered in translating to therapeutic modalities. It is increasingly apparent that an integrative examination of the molecular underpinnings of cell death is imperative for advancing the field, particularly within the framework of inter-pathway functional synergy. In this review, we provide an overview of various forms of RCD, including autophagy-dependent cell death, anoikis, ferroptosis, cuproptosis, pyroptosis and immunogenic cell death. We summarize the latest advancements in understanding the molecular mechanisms that regulate RCD in glioma and explore the interconnections between different cell death processes. By comprehending these connections and developing targeted strategies, we have the potential to enhance glioma therapy through manipulation of RCD.
神经胶质瘤是起源于中枢神经系统的原发性肿瘤。神经胶质瘤的传统治疗方案通常包括手术切除和替莫唑胺（TMZ）化疗。然而，尽管采取了积极的干预措施，神经胶质瘤患者的中位生存期仅约为14.6个月。因此，迫切需要探索治疗神经胶质瘤的创新治疗策略。调节性细胞死亡（RCD）的基础研究可以追溯到1842年卡尔·沃格特（Karl Vogt）对蟾蜍细胞死亡的开创性观察。在过去十年中，细胞死亡命名委员会（NCCD）对细胞死亡的各种形式和机制进行了系统分类和描述，综合了形态学、生物化学和功能特征。细胞死亡主要表现为两种形式：意外细胞死亡（ACD），由物理、化学或机械破坏等外部因素引起；以及RCD，这是一个基因导向的内在过程，可根据生理和病理信号协调细胞的有序死亡。我们对RCD的理解进展揭示了操纵细胞死亡调节——无论是通过诱导还是抑制——作为肿瘤学中一种潜在的突破性方法，具有重大前景。然而，在研究与临床应用的界面上仍然存在障碍，在转化为治疗模式时遇到了重大阻碍。越来越明显的是，对细胞死亡分子基础进行综合研究对于推动该领域发展至关重要，特别是在通路间功能协同的框架内。在这篇综述中，我们概述了RCD的各种形式，包括自噬依赖性细胞死亡、失巢凋亡、铁死亡、铜死亡、焦亡和免疫原性细胞死亡。我们总结了在理解神经胶质瘤中调节RCD的分子机制方面的最新进展，并探讨了不同细胞死亡过程之间的相互联系。通过理解这些联系并制定针对性策略，我们有可能通过操纵RCD来增强神经胶质瘤的治疗效果。
