Strategies in gene therapy for glioblastoma.

Strategies in gene therapy for glioblastoma.
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DOI:
10.3390/cancers5041271
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发表时间:
2013-10-23
期刊:
影响因子:
5.2
通讯作者:
Viapiano, Mariano S
Viapiano, Mariano S
中科院分区:
医学2区
文献类型:
--
作者:
Kwiatkowska, Aneta;Nandhu, Mohan S;Viapiano, Mariano S

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胶质母细胞瘤(GBM)是最具侵袭性的脑癌,预后不良,存活率极低。迫切需要新的治疗方法来改善这些肿瘤的临床管理并延长患者的生存期。GBM的基因疗法已经被假定并尝试了二十年,在临床前模型和临床试验中取得了不同程度的成功。在这里,我们回顾了最常见的方法来治疗GBM的基因治疗,包括策略,提供肿瘤抑制基因,自杀基因,免疫调节细胞因子,以提高免疫反应,和条件复制溶瘤病毒。综述的重点是用于基因递送的策略,包括最常见和最广泛使用的载体(即,复制型和非复制型病毒)以及新的治疗方法,如干细胞介导的治疗和用于基因递送的纳米技术。我们提出了这些战略的概述,他们的目标,不同的优势,以及成功的挑战。最后,我们讨论了基因治疗为基础的策略,有效地攻击这样一个复杂的遗传靶点GBM,单独或与常规治疗相结合的潜力。
Glioblastoma (GBM) is the most aggressive form of brain cancer, with a dismal prognosis and extremely low percentage of survivors. Novel therapies are in dire need to improve the clinical management of these tumors and extend patient survival. Genetic therapies for GBM have been postulated and attempted for the past twenty years, with variable degrees of success in pre-clinical models and clinical trials. Here we review the most common approaches to treat GBM by gene therapy, including strategies to deliver tumor-suppressor genes, suicide genes, immunomodulatory cytokines to improve immune response, and conditionally-replicating oncolytic viruses. The review focuses on the strategies used for gene delivery, including the most common and widely used vehicles (i.e., replicating and non-replicating viruses) as well as novel therapeutic approaches such as stem cell-mediated therapy and nanotechnologies used for gene delivery. We present an overview of these strategies, their targets, different advantages, and challenges for success. Finally, we discuss the potential of gene therapy-based strategies to effectively attack such a complex genetic target as GBM, alone or in combination with conventional therapy.