Department of Neuro-Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Semin Oncol. 2011 Dec;38 Suppl 4:S21-33. doi: 10.1053/j.seminoncol.2011.09.008.
Despite international efforts, the treatment of recurrent glioblastoma (GBM) remains challenging. Although advances in surgical resection, the use of radiotherapy, and, predominantly, improved medical therapies have led to incremental improvements in median survival, few options exist for the management of recurrent or resistant disease. Insight into the molecular pathogenesis of GBM has led to the recent development of targeted therapeutic strategies aimed at the interruption of key molecular signaling pathways. However, due to the complex and redundant activation of the signaling mechanisms in GBM tumors, the evaluation of targeted agents in clinical trials has been largely limited. The ongoing effort to identify effective strategies for the treatment of recurrent GBM includes combination strategies with agents that target complementary or redundant pathways. Incorporation of novel trial designs that permit simultaneous evaluation of several agent combinations and allow for rapid discontinuation of ineffective regimens can accelerate the clinical evaluation of such candidate regimens. This review discusses strategies and outcomes of existing and emerging treatment approaches, and the challenges associated with the integration of novel therapies into clinical practice.
尽管国际上做出了努力，但复发性脑胶质瘤（GBM）的治疗仍然具有挑战性。尽管手术切除、放疗的进步，以及主要的、改进的医疗治疗方法已经导致中位生存期的逐渐改善，但对于复发性或耐药性疾病的治疗，几乎没有选择。对 GBM 分子发病机制的深入了解导致了最近靶向治疗策略的发展，旨在阻断关键的分子信号通路。然而，由于 GBM 肿瘤中信号机制的复杂和冗余激活，靶向药物在临床试验中的评估在很大程度上受到限制。目前正在努力寻找治疗复发性 GBM 的有效策略，包括与靶向互补或冗余途径的药物联合治疗策略。采用新的试验设计，可以同时评估几种药物联合使用，并允许快速停止无效方案，可以加速对这些候选方案的临床评估。这篇综述讨论了现有和新兴治疗方法的策略和结果，以及将新疗法纳入临床实践所面临的挑战。
