Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United States; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, United States; Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, United States.
Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United States; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, United States; Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, United States; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States.
Handb Clin Neurol. 2024;205:297-315. doi: 10.1016/B978-0-323-90120-8.00009-5.
The majority of primary brain tumors are gliomas, among which glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. GBM has a median survival of 18-24 months, and despite extensive research it remains incurable, thus novel therapies are urgently needed. The current standard of care is a combination of surgery, radiation, and chemotherapy, but still remains ineffective due to the invasive nature and high recurrence of gliomas. Gene therapy is a versatile treatment strategy investigated for multiple tumor types including GBM. In gene therapy, a variety of vectors are employed to deliver genes designed for different antitumoral effects. Also, over the past decades, stem cell biology has provided a new approach to cancer therapies. Stem cells can be used as regenerative medicine, therapeutic carriers, drug targeting, and generation of immune cells. Stem cell-based therapy allows targeted therapy that spares healthy brain tissue as well as establishes a long-term antitumor response by stimulating the immune system and delivering prodrug, metabolizing genes, or even oncolytic viruses. This chapter describes the latest developments and the current trends in gene and cell-based therapy against GBM from both preclinical and clinical perspectives, including different gene therapy delivery systems, molecular targets, and stem cell therapies.
大多数原发性脑肿瘤是神经胶质瘤，其中多形性胶质母细胞瘤（GBM）是成人中最常见的恶性脑肿瘤。GBM 的中位生存期为 18-24 个月，尽管进行了广泛的研究，但仍然无法治愈，因此迫切需要新的治疗方法。目前的标准治疗方法是手术、放疗和化疗的结合，但由于神经胶质瘤的侵袭性和高复发率，仍然效果不佳。基因治疗是一种针对多种肿瘤类型（包括 GBM）的多用途治疗策略。在基因治疗中，使用多种载体来传递设计用于不同抗肿瘤效果的基因。此外，在过去几十年中，干细胞生物学为癌症治疗提供了一种新方法。干细胞可用作再生医学、治疗载体、药物靶向和免疫细胞的产生。基于干细胞的治疗允许靶向治疗，从而避免健康脑组织，并通过刺激免疫系统和递送前药、代谢基因甚至溶瘤病毒来建立长期的抗肿瘤反应。本章从临床前和临床角度描述了针对 GBM 的基因和基于细胞的治疗的最新进展和当前趋势，包括不同的基因治疗传递系统、分子靶点和干细胞治疗。
