Paw Ivy, Carpenter Richard C, Watabe Kounosuke, Debinski Waldemar, Lo Hui-Wen
Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA; Brain Tumor Center of Excellence, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA; Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Cancer Lett. 2015 Jun 28;362(1):1-7. doi: 10.1016/j.canlet.2015.03.015. Epub 2015 Mar 18.
Glioblastoma (GBM) is the most aggressive, deadliest, and most common brain malignancy in adults. Despite the advances made in surgical techniques, radiotherapy and chemotherapy, the median survival for GBM patients has remained at a mere 14 months. GBM poses several unique challenges to currently available treatments for the disease. For example, GBM cells have the propensity to aggressively infiltrate/invade into the normal brain tissues and along the vascular tracks, which prevents complete resection of all malignant cells and limits the effect of localized radiotherapy while sparing normal tissue. Although anti-angiogenic treatment exerts anti-edematic effect in GBM, unfortunately, tumors progress with acquired increased invasiveness. Therefore, it is an important task to gain a deeper understanding of the intrinsic and post-treatment invasive phenotypes of GBM in hopes that the gained knowledge would lead to novel GBM treatments that are more effective and less toxic. This review will give an overview of some of the signaling pathways that have been shown to positively and negatively regulate GBM invasion, including, the PI3K/Akt, Wnt, sonic hedgehog-GLI1, and microRNAs. The review will also discuss several approaches to cancer therapies potentially altering GBM invasiveness.
胶质母细胞瘤(GBM)是成人中最具侵袭性、最致命且最常见的脑恶性肿瘤。尽管在手术技术、放疗和化疗方面取得了进展,但GBM患者的中位生存期仅为14个月。GBM给目前针对该疾病的治疗带来了诸多独特挑战。例如,GBM细胞倾向于侵袭正常脑组织并沿血管路径浸润,这使得无法完全切除所有恶性细胞,限制了局部放疗的效果,同时保护了正常组织。尽管抗血管生成治疗在GBM中发挥抗水肿作用,但不幸的是,肿瘤会随着侵袭性增加而进展。因此,更深入地了解GBM的内在和治疗后侵袭表型是一项重要任务,希望所获得的知识能带来更有效且毒性更小的新型GBM治疗方法。本综述将概述一些已被证明对GBM侵袭具有正向和负向调节作用的信号通路,包括PI3K/Akt、Wnt、音猬因子-GLI1和微小RNA。该综述还将讨论几种可能改变GBM侵袭性的癌症治疗方法。