Departamento de Neuroinmunología, Laboratorio de Neurobiología Molecular y Celular, Laboratorio Experimental de Enfermedades Neurodegenerativas del Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", C.P. 14269 Ciudad de México, Mexico.
Hospital Regional de Alta Especialidad de Oaxaca, Secretaria de Salud, C.P. 71256 Oaxaca, Mexico.
Int J Mol Sci. 2018 Nov 27;19(12):3773. doi: 10.3390/ijms19123773.
Glioblastoma multiforme is the most malignant and aggressive type of brain tumor, with a mean life expectancy of less than 15 months. This is due in part to the high resistance to apoptosis and moderate resistant to autophagic cell death in glioblastoma cells, and to the poor therapeutic response to conventional therapies. Autophagic cell death represents an alternative mechanism to overcome the resistance of glioblastoma to pro-apoptosis-related therapies. Nevertheless, apoptosis induction plays a major conceptual role in several experimental studies to develop novel therapies against brain tumors. In this review, we outline the different components of the apoptotic and autophagic pathways and explore the mechanisms of resistance to these cell death pathways in glioblastoma cells. Finally, we discuss drugs with clinical and preclinical use that interfere with the mechanisms of survival, proliferation, angiogenesis, migration, invasion, and cell death of malignant cells, favoring the induction of apoptosis and autophagy, or the inhibition of the latter leading to cell death, as well as their therapeutic potential in glioma, and examine new perspectives in this promising research field.
多形性胶质母细胞瘤是最恶性和侵袭性的脑肿瘤,平均预期寿命不到 15 个月。这部分是由于胶质母细胞瘤细胞对细胞凋亡的高抵抗力和对自噬性细胞死亡的中度抵抗,以及对传统疗法的治疗反应不佳。自噬性细胞死亡代表了克服胶质母细胞瘤对与促进细胞凋亡相关的治疗的抗性的另一种机制。然而,凋亡诱导在几种实验研究中发挥了重要的概念作用,以开发针对脑肿瘤的新疗法。在这篇综述中,我们概述了凋亡和自噬途径的不同组成部分,并探讨了胶质母细胞瘤细胞对这些细胞死亡途径的抗性机制。最后,我们讨论了具有临床和临床前用途的药物,这些药物干扰恶性细胞的存活、增殖、血管生成、迁移、侵袭和细胞死亡的机制,有利于诱导细胞凋亡和自噬,或抑制后者导致细胞死亡,以及它们在神经胶质瘤中的治疗潜力,并研究了这一有前途的研究领域的新视角。