Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
Neuro Oncol. 2014 Mar;16(3):334-51. doi: 10.1093/neuonc/not310. Epub 2014 Jan 26.
Despite extensive research, current glioma therapies are still unsatisfactory, and novel approaches are pressingly needed. In recent years, both nonreplicative viral vectors and replicating oncolytic viruses have been developed for brain cancer treatment, and the mechanistic background of their cytotoxicity has been unveiled. A growing number of clinical trials have convincingly established viral therapies to be safe in glioma patients, and maximum tolerated doses have generally not been reached. However, evidence for therapeutic benefit has been limited: new generations of therapeutic vectors need to be developed in order to target not only tumor cells but also the complex surrounding microenvironment. Such therapies could also direct long-lasting immune responses toward the tumor while reducing early antiviral reactions. Furthermore, viral delivery methods are to be improved and viral spread within the tumor will have to be enhanced. Here, we will review the outcome of completed glioma virus therapy trials as well as highlight the ongoing clinical activities. On this basis, we will give an overview of the numerous strategies to enhance therapeutic efficacy of new-generation viruses and novel treatment regimens. Finally, we will conclude with approaches that may be crucial to the development of successful glioma therapies in the future.
尽管已经进行了广泛的研究，但目前的胶质瘤治疗方法仍不尽如人意，迫切需要新的方法。近年来，非复制型病毒载体和复制型溶瘤病毒已被开发用于脑癌治疗，其细胞毒性的机制背景已被揭示。越来越多的临床试验令人信服地证实了病毒疗法在胶质瘤患者中的安全性，而且一般尚未达到最大耐受剂量。然而，治疗效果的证据有限：需要开发新一代的治疗性载体，不仅要针对肿瘤细胞，还要针对复杂的周围微环境。此类疗法还可以针对肿瘤引导持久的免疫反应，同时减少早期抗病毒反应。此外，还需要改进病毒传递方法，并增强病毒在肿瘤内的传播。在这里，我们将回顾已完成的胶质瘤病毒治疗试验的结果，并重点介绍正在进行的临床活动。在此基础上，我们将概述增强新一代病毒和新治疗方案治疗效果的众多策略。最后，我们将总结未来成功治疗胶质瘤可能至关重要的方法。
