Center for Neurology and Neurosurgery, Goethe University Hospital, Goethe University, Frankfurt, Germany.
Anticancer Agents Med Chem. 2010 Jul;10(6):438-49. doi: 10.2174/1871520611009060438.
Induction of caspase-dependent apoptosis (type I cell death) is a major mechanism by which most chemotherapeutic drugs and radiation kill tumor cells. However, conventional cancer therapies fail to mediate their effects in a target-specific fashion. The extremely unfavorable prognosis for patients suffering from glioblastomas (GBMs) is strongly correlated to the intrinsic apoptosis resistance of GBM cells which especially occurs in diffusely migrating tumor cells. The ultimate goal for molecular, apoptosis-based therapies is to target specific components of the two major apoptotic pathways, i.e. the extrinsic and the intrinsic pathway to trigger tumor-selective apoptosis, while at the same time limiting toxicity in normal tissues. Induction of autophagic cell death (type II cell death) by pro-autophagic drugs is an alternative and emerging concept to trigger glioma cell death and to exploit caspase-independent programmed cell death pathways for the development of novel glioma therapies. This review provides an up to date and comprehensive report on the relevant pre-clinical and clinical drugs interfering with the major apoptosis and autophagy pathways, their therapeutic potential in glioma and adresses potential future perspectives in this exciting field of research.
诱导 caspase 依赖性细胞凋亡（I 型细胞死亡）是大多数化疗药物和辐射杀死肿瘤细胞的主要机制。然而，传统的癌症疗法无法以靶向特异性的方式发挥作用。患有胶质母细胞瘤 (GBM) 的患者预后极差，这与 GBM 细胞固有的细胞凋亡抵抗密切相关，尤其是在弥漫性迁移的肿瘤细胞中。基于分子的细胞凋亡疗法的最终目标是靶向两种主要凋亡途径的特定成分，即外在途径和内在途径，以触发肿瘤选择性细胞凋亡，同时限制正常组织的毒性。通过促自噬药物诱导自噬性细胞死亡（II 型细胞死亡）是触发神经胶质瘤细胞死亡和利用无 caspase 依赖性程序性细胞死亡途径开发新型神经胶质瘤治疗方法的另一种新兴概念。本文综述了目前关于干扰主要凋亡和自噬途径的相关临床前和临床药物的最新和全面的报告，及其在神经胶质瘤中的治疗潜力，并探讨了该研究领域中令人兴奋的未来展望。
