University of Washington, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, 825 Eastlake Ave E, POB 19023, MS G4-940, Seattle, WA 98109-1023, USA.
Expert Rev Neurother. 2011 Apr;11(4):519-32. doi: 10.1586/ern.11.30.
Despite recent advances, there remains an unmet need for more effective treatments for newly diagnosed and recurrent glioblastoma (GBM). While currently available alkylator-based and antiangiogenic agents provide some efficacy, novel antiangiogenic and antiglioma treatments that provide enhanced efficacy with improvements in overall survival, the potential to overcome drug resistance and decreased treatment-related toxicity are still needed. Although VEGF-directed angiogenesis is critical during GBM pathogenesis, alternative proangiogenic and glioma-promoting pathways also play a key role in tumor progression. This article reviews the limitations of current GBM treatment, the importance of angiogenic signaling pathways in GBM pathogenesis and the preliminary results of novel antiangiogenic-targeted treatments being evaluated in GBM. Therapies that inhibit multiple glioma signaling pathways, including angiogenesis, have the possibility for further improving outcome in GBM and may represent the best option for increasing overall survival.
尽管最近取得了一些进展,但对于新诊断和复发性胶质母细胞瘤(GBM),仍需要更有效的治疗方法。虽然目前可用的烷化剂和抗血管生成药物具有一定的疗效,但仍需要新型的抗血管生成和抗胶质瘤治疗方法,以提高疗效,改善总生存期,有潜力克服耐药性并降低治疗相关毒性。尽管 VEGF 导向的血管生成在 GBM 发病机制中至关重要,但替代的促血管生成和促进胶质瘤的途径也在肿瘤进展中发挥关键作用。本文综述了目前 GBM 治疗的局限性、血管生成信号通路在 GBM 发病机制中的重要性以及正在 GBM 中评估的新型抗血管生成靶向治疗的初步结果。抑制包括血管生成在内的多种胶质瘤信号通路的治疗方法有可能进一步改善 GBM 的预后,并可能成为提高总生存期的最佳选择。