Targeting Glucose Promising for Glioblastoma Therapy

A novel combination therapy that targets glucose in the brain was effective in mouse models of glioblastoma, an aggressive and deadly form of brain cancer, according to a study published by Nature Medicine.

The investigational drug works by interrupting and exploiting glucose intake, which inhibits the cancer’s nutrients and energy. The treatment also triggers cell death pathways and prevents the tumor from growing.

Since the survival rate of glioblastoma is only 15 months in adults, novel therapies against the cancer are severely needed, according to the authors.

Previous studies have shown that common mutations in glioblastoma promote glucose intake. Since normal brain function and tissue repair require glucose, targeting sugar directly would result in significant adverse events, according to the authors.

The combination therapy includes the FDA-approved erlotinib, which targets EGFR that is commonly mutated in glioblastoma. The authors found that erlotinib reduces glucose uptake in glioblastoma and makes cancer metabolically vulnerable, according to the study.

The investigators then attacked the glucose deficit with idasanutlin, an experimental drug that activates the P53 protein. This protein promotes cell death and triggers tumor regression, which may be a crucial component of a glioblastoma drug, according to the authors.

Included in the study were 19 glioblastoma cells from human patients that were implanted into mice models of the disease. The authors used PET imaging to examine the drug’s effects and assays to determine when cancer cells die as a result of targeting glucose metabolism.

The results suggest that the combination treatment may be able to effectively target glucose metabolism and induce cell death in glioblastoma.

The authors also discovered that PET scans can predict which patients would respond to the investigational combination, according to the study.

Next, the authors plan to test the combination therapy in human patients with glioblastoma. Since part of the treatment has already been approved by the FDA, it may be able to quickly advance in clinical testing. The authors concluded that they may be able to design a novel strategy that would effectively attack and kill glioblastoma to reduce the risk of recurrence.