Gene therapy for malignant glioma.
Gene therapy for malignant glioma.
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DOI：
10.1186/2052-8426-2-21
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Rutka JT
中科院分区：
文献类型：
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作者：
Okura H;Smith CA;Rutka JT
多形性胶质母细胞瘤（GBM）是成人中最常见和最具破坏性的原发性脑肿瘤。尽管目前的治疗方式，如手术切除后化疗和放疗，中位生存期只有适度的改善。胶质瘤干细胞对常规治疗的抵抗可能导致GBM的频繁复发和侵袭性；因此，迫切需要新的替代治疗策略。分子生物学和基因技术的最新进展为GBM患者提供了有吸引力的新治疗可能性。基因治疗被定义为一种旨在改变细胞的遗传补体以获得治疗效果的技术。迄今为止，用于治疗GBM的基因疗法已在临床前研究中显示出抗肿瘤效果，并在临床研究中显示出良好的安全性。然而，尽管这种方法显然很有前途，但仍然存在与转导效率、病毒传递、大脑病理反应和治疗效果相关的问题。肿瘤的发展和进展涉及广泛的基因谱的改变，因此各种基因治疗GBM的方法已被提出。正在评估改进的病毒载体，并正在研究单独使用基因治疗或与其他治疗协同作用治疗GBM的可能性。在这篇综述中，我们将讨论在临床前和临床研究中最常用的治疗GBM的基因治疗方法，包括：药物前/自杀基因治疗；溶瘤基因治疗；细胞因子介导的基因治疗；以及肿瘤抑制基因疗法。此外，我们还综述了目前基因治疗策略的原理和机制，以及每种策略的优缺点。
Glioblastoma multiforme (GBM) is the most frequent and devastating primary brain tumor in adults. Despite current treatment modalities, such as surgical resection followed by chemotherapy and radiotherapy, only modest improvements in median survival have been achieved. Frequent recurrence and invasiveness of GBM are likely due to the resistance of glioma stem cells to conventional treatments; therefore, novel alternative treatment strategies are desperately needed. Recent advancements in molecular biology and gene technology have provided attractive novel treatment possibilities for patients with GBM. Gene therapy is defined as a technology that aims to modify the genetic complement of cells to obtain therapeutic benefit. To date, gene therapy for the treatment of GBM has demonstrated anti-tumor efficacy in pre-clinical studies and promising safety profiles in clinical studies. However, while this approach is obviously promising, concerns still exist regarding issues associated with transduction efficiency, viral delivery, the pathologic response of the brain, and treatment efficacy. Tumor development and progression involve alterations in a wide spectrum of genes, therefore a variety of gene therapy approaches for GBM have been proposed. Improved viral vectors are being evaluated, and the potential use of gene therapy alone or in synergy with other treatments against GBM are being studied. In this review, we will discuss the most commonly studied gene therapy approaches for the treatment of GBM in preclinical and clinical studies including: prodrug/suicide gene therapy; oncolytic gene therapy; cytokine mediated gene therapy; and tumor suppressor gene therapy. In addition, we review the principles and mechanisms of current gene therapy strategies as well as advantages and disadvantages of each.