Alemany Montse, Bruna Jordi, Yuste Victor J
Cell Death, Senescence and Survival Group, Departament de Bioquímica i Biologia Molecular and Institut de Neurociències, Facultat de Medicina, Universitat Autònoma de Barcelona, Campus de Bellaterra, Bellaterra, Spain.
Neuro-Oncology Unit, Hospital Universitari de Bellvitge-ICO L'Hospitalet (IDIBELL), Barcelona, Spain.
Neurooncol Adv. 2025 Aug 6;7(1):vdaf174. doi: 10.1093/noajnl/vdaf174. eCollection 2025 Jan-Dec.
The activation of cellular death programs does not necessarily predetermine an inevitable outcome. Identifying the precise moment when a cell irreversibly transitions from life to death presents a significant challenge in its assessment and measurement. In this review, we explore the critical alterations in cellular structures that have been proposed as the . Using glioblastoma as a model-one of the most aggressive and lethal tumor types with a remarkable ability to evade cell death-we highlight the challenge of reaching the . Glioblastoma cells often exhibit impaired function of the apoptotic endonuclease, DFF40/CAD/CPAN, leading to incomplete apoptosis and genomic instability. The sublethal activation of DFF40/CAD/CPAN not only allows tumor cells to survive but can also drive more aggressive phenotypes and enhance therapeutic resistance. We underscore the need to reassess glioblastoma treatment strategies from broad cytotoxic approaches to more targeted therapies that exploit specific vulnerabilities within regulated cell death (RCD) pathways.
细胞死亡程序的激活并不一定预示着不可避免的结果。确定细胞从生命不可逆地转变为死亡的确切时刻，在其评估和测量方面是一项重大挑战。在本综述中，我们探讨了被认为是……的细胞结构中的关键改变。以胶质母细胞瘤为模型——这是最具侵袭性和致命性的肿瘤类型之一，具有显著的逃避细胞死亡的能力——我们强调了达成……的挑战。胶质母细胞瘤细胞通常表现出凋亡核酸内切酶DFF40/CAD/CPAN功能受损，导致凋亡不完全和基因组不稳定。DFF40/CAD/CPAN的亚致死激活不仅使肿瘤细胞得以存活，还可驱动更具侵袭性的表型并增强治疗抗性。我们强调有必要重新评估胶质母细胞瘤的治疗策略，从广泛的细胞毒性方法转向利用调节性细胞死亡（RCD）途径中特定脆弱性的更具针对性的疗法。
