Introduction: Despite decades of clinical trials utilizing conventional and novel therapeutics, the effective treatment of glioblastoma remains one of the most formidable challenges in oncology. Current standard of care includes surgery and chemoradiation. Synthetic pharmacotherapies continue to be explored as potential therapeutic options for glioblastoma patients.Areas covered: This study reviews synthetic pharmacotherapies that are currently under investigation in phase I-III clinical trials. The authors of this study highlight the mechanisms of action of the synthetic pharmacotherapy agents under investigation, outline the available evidence for their utility based on the literature, and summarize the current landscape.Expert opinion: Although warranting further investigation, the studies generally highlighted here have not shown remarkable changes in clinical benefits beyond what has already been established with radiochemotherapy. As we develop more synthetics, we will likely need to combine them with other synthetics to target multiple separate molecular pathways. There is considerable potential when this treatment strategy is guided by molecular profiling approaches which seek to stratify patients based on treatments that would be most efficacious for them.
Keywords: Glioblastoma; clinical trials; high-grade glioma; malignant glioma; small molecule inhibitors; targeted therapy; tyrosine kinase inhibitors.