Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
J Neurooncol. 2021 Jan;151(2):103-112. doi: 10.1007/s11060-020-03671-w. Epub 2021 Jan 4.
Glioblastoma (GBM) is the most fatal brain tumor in adults. Current survival rates of GBM remain below 2 years due to GBM's aggressive cellular migration and genetically driven treatment escape pathways. Despite our rapidly increasing understanding of GBM biology, earlier diagnoses, and refined surgical techniques, only moderate survival benefits have been achieved. Nonetheless, the pressing need for better survival rates has brought forward a multitude of newer therapeutic approaches and opened the door for potential personalization of these modalities in the near future.
We reviewed the published literature discussing the current state of knowledge regarding GBM biology and therapy and summarized the information that may point toward future personalized therapeutic strategies.
Several novel modalities such as oncolytic viruses, targeted immune, and molecular therapies, and tumor treating fields have been introduced. To date, there is no single treatment modality for GBM, but rather a wide spectrum of combined modalities that address intratumoral cellular and genetic variabilities. While the current state of GBM research and clinical trial landscape may hold promise, current literature lacks any fruitful progress towards personalized GBM therapy.
In this review, we are discussing our recent knowledge of the GBM genetic biologic landscape and the current advances in therapy, as well as providing a blueprint for an envisioned GBM management paradigm that should be personalized and adaptable to accommodate each patient's diverse genetic variations and therapy response/escape patterns.
胶质母细胞瘤(GBM)是成人中最致命的脑肿瘤。由于 GBM 具有侵袭性的细胞迁移和遗传驱动的治疗逃逸途径,目前 GBM 的生存率仍低于 2 年。尽管我们对 GBM 生物学、早期诊断和精细手术技术的理解迅速增加,但仅取得了适度的生存获益。尽管如此,对更高生存率的迫切需求带来了许多新的治疗方法,并为这些方法在不久的将来实现潜在的个性化开辟了道路。
我们回顾了已发表的文献,讨论了目前关于 GBM 生物学和治疗的知识状况,并总结了可能指向未来个性化治疗策略的信息。
已经引入了几种新型治疗方法,如溶瘤病毒、靶向免疫和分子治疗以及肿瘤治疗电场等。迄今为止,GBM 没有单一的治疗方法,而是广泛采用多种联合治疗方法来解决肿瘤内细胞和遗传变异性。虽然目前 GBM 研究和临床试验的现状可能有希望,但目前的文献缺乏任何朝着个性化 GBM 治疗方向的实质性进展。
在这篇综述中,我们讨论了我们对 GBM 遗传生物学景观的最新认识和目前在治疗方面的进展,并为想象中的 GBM 管理范式提供了蓝图,该范式应个性化且能够适应每个患者的不同遗传变异和治疗反应/逃逸模式。