Recurrent glioblastoma: a fresh look at current therapies and emerging novel approaches.

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.