Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China.
Curr Med Chem. 2013;20(15):1974-84. doi: 10.2174/0929867311320150004.
Glioblastoma multiforme (GBM) is known to be the most common and lethal malignant primary brain tumor. Despite vigorous basic and clinical studies over the past decades, the prognosis of patients with GBM has remained dismal. The fundamental problem with these malignancies occurs due to tumor cells' highly infiltrative nature, precluding a complete surgical resection, and a productive or acquired resistance to cytotoxic therapy. Recent studies demonstrated that GBMs exhibited remarkable cellular heterogeneity and hierarchy containing self-renewing glioma stem cells (GSCs). The malignant growth of GBM can be propagated and sustained by GSCs that are endowed with highly efficient clonogenic and tumor initiation capacities. GSCs can be identified with technical support and are responsible for the invasive potential and recurrence of GBMs. They share core signaling pathways with normal neural stem cells, but also display critical distinctions that provide important clues for useful therapeutic targets. Therefore, targeting GSCs becomes priorities for the development of novel therapeutic paradigms. Herein, we reviewed the existing and promising targeting therapies for GSCs which could effectively inhibit the tumor invasion, proliferation and recurrence of GBMs. Significant features of GSCs, such as invasive growth pattern, angiogenic potential, resistance to traditional therapy and differentiation, are important therapeutic targets. More promising strategies should target GSCs themselves by taking advantages of highthroughput technologies and dissecting the intrinsic molecular nature of GSCs. Novel chemical medicines targeting these GSCs may represent one of the most important directions. Hopefully, this could shed a light on the path we are going to.
多形性胶质母细胞瘤（GBM）是最常见和致命的恶性原发性脑肿瘤。尽管在过去几十年中进行了大量的基础和临床研究，但 GBM 患者的预后仍然很差。这些恶性肿瘤的根本问题是由于肿瘤细胞具有高度浸润性，无法进行完全的手术切除，以及对细胞毒性治疗产生或获得耐药性。最近的研究表明，GBM 表现出显著的细胞异质性和层次结构，其中包含自我更新的神经胶质瘤干细胞（GSCs）。GBM 的恶性生长可以通过具有高效克隆形成和肿瘤起始能力的 GSCs 来繁殖和维持。GSCs 可以通过技术支持来识别，并且负责 GBM 的侵袭潜力和复发。它们与正常神经干细胞共享核心信号通路，但也显示出重要的区别，为有用的治疗靶点提供了重要线索。因此，针对 GSCs 成为开发新治疗模式的重点。本文综述了现有的和有前途的针对 GSCs 的靶向治疗方法，这些方法可以有效地抑制 GBM 的肿瘤侵袭、增殖和复发。GSCs 的显著特征，如侵袭性生长模式、血管生成潜力、对传统治疗的耐药性和分化，是重要的治疗靶点。更有前途的策略应该利用高通量技术靶向 GSCs 本身，并剖析 GSCs 的内在分子特性。针对这些 GSCs 的新型化学药物可能代表了最重要的方向之一。希望这能为我们指明前进的道路。
