Parenteral high-dose ascorbate - A possible approach for the treatment of glioblastoma (Review)

For glioblastoma, the treatment with standard of care therapy comprising resection, radiation, and temozolomide results in overall survival of approximately 14-18 months after initial diagnosis. Even though several new therapy approaches are under investigation, it is difficult to achieve life prolongation and/or improvement of patient's quality of life. The aggressiveness and progression of glioblastoma is initially orchestrated by the biological complexity of its genetic phenotype and ability to respond to cancer therapy via changing its molecular patterns, thereby developing resistance. Recent clinical studies of pharmacological ascorbate have demonstrated its safety and potential efficacy in different cancer entities regarding patient's quality of life and prolongation of survival. In this review article, the actual glioblastoma treatment possibilities are summarized, the evidence for pharmacological ascorbate in glioblastoma treatment is examined and questions are posed to identify current gaps of knowledge regarding accessibility of ascorbate to the tumor area. Experiments with glioblastoma cell lines and tumor xenografts have demonstrated that high-dose ascorbate induces cytotoxicity and oxidative stress largely selectively in malignant cells compared to normal cells suggesting ascorbate as a potential therapeutic agent. Further investigations in larger cohorts and randomized placebo-controlled trials should be performed to confirm these findings as well as to improve delivery strategies to the brain, through the inherent barriers and ultimately to the malignant cells.