Hulou M Maher, Cho Choi-Fong, Chiocca E Antonio, Bjerkvig Rolf
Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Handb Clin Neurol. 2016;134:183-97. doi: 10.1016/B978-0-12-802997-8.00011-6.
Glioblastoma is the most common and aggressive primary brain tumor in adults. Over the past three decades, the overall survival time has only improved by a few months, therefore novel alternative treatment modalities are needed to improve clinical management strategies. Such strategies should ultimately extend patient survival. At present, the extensive insight into the molecular biology of gliomas, as well as into genetic engineering techniques, has led to better decision processes when it comes to modifying the genome to accommodate suicide genes, cytokine genes, and tumor suppressor genes that may kill cancer cells, and boost the host defensive immune system against neoantigenic cytoplasmic and nuclear targets. Both nonreplicative viral vectors and replicating oncolytic viruses have been developed for brain cancer treatment. Stem cells, microRNAs, nanoparticles, and viruses have also been designed. These have been armed with transgenes or peptides, and have been used both in laboratory-based experiments as well as in clinical trials, with the aim of improving selective killing of malignant glioma cells while sparing normal brain tissue. This chapter reviews the current status of gene therapies for malignant gliomas and highlights the most promising viral and cell-based strategies under development.
胶质母细胞瘤是成人中最常见且侵袭性最强的原发性脑肿瘤。在过去三十年里，总体生存时间仅延长了几个月，因此需要新的替代治疗方式来改进临床管理策略。此类策略最终应能延长患者生存期。目前，对胶质瘤分子生物学以及基因工程技术的深入了解，在修改基因组以容纳自杀基因、细胞因子基因和肿瘤抑制基因方面带来了更好的决策过程，这些基因可能杀死癌细胞，并增强宿主针对新抗原性细胞质和核靶点的防御免疫系统。非复制型病毒载体和复制型溶瘤病毒均已被开发用于脑癌治疗。干细胞、微小RNA、纳米颗粒和病毒也已被设计出来。它们被装载了转基因或肽，并已用于基于实验室的实验以及临床试验，目的是在 sparing normal brain tissue的同时提高对恶性胶质瘤细胞的选择性杀伤。本章回顾了恶性胶质瘤基因治疗的现状，并突出了正在开发的最有前景的基于病毒和细胞的策略。 （注：原文中“sparing normal brain tissue”表述有误，可能是“sparing normal brain tissues”，意为“ sparing正常脑组织”）
