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Simple Summary  Glioblastoma is a devastating malignancy that has continued to prove resistant to a variety of therapeutics. No new systemic therapy has been approved for use against glioblastoma in almost two decades. This observation is particularly disturbing given the amount of money invested in identifying novel therapies for this disease. A relatively rapid and economical pipeline for identification of novel agents is drug repurposing. Here, a comprehensive review detailing the state of drug repurposing in glioblastoma is provided. We reveal details on studies that have examined agents in vitro, in animal models and in patients. While most agents have not progressed beyond the initial stages, several drugs, from a variety of classes, have demonstrated promising results in early phase clinical trials.    Abstract  The treatment of glioblastoma (GBM) remains a significant challenge, with outcome for most pa-tients remaining poor. Although novel therapies have been developed, several obstacles restrict the incentive of drug developers to continue these efforts including the exorbitant cost, high failure rate and relatively small patient population. Repositioning drugs that have well-characterized mechanistic and safety profiles is an attractive alternative for drug development in GBM. In ad-dition, the relative ease with which repurposed agents can be transitioned to the clinic further supports their potential for examination in patients. Here, a systematic analysis of the literature and clinical trials provides a comprehensive review of primary articles and unpublished trials that use repurposed drugs for the treatment of GBM. The findings demonstrate that numerous drug classes that have a range of initial indications have efficacy against preclinical GBM models and that certain agents have shown significant potential for clinical benefit. With examination in randomized, placebo-controlled trials and the targeting of particular GBM subgroups, it is pos-sible that repurposing can be a cost-effective approach to identify agents for use in multimodal anti-GBM strategies.

An Alternative Pipeline for Glioblastoma Therapeutics: A Systematic Review of Drug Repurposing in Glioblastoma