Researchers at the UCLA Jonsson Comprehensive Cancer Center have identified a new way to improve survival rates in treating glioblastoma, one of the deadliest and most difficult-to-treat brain tumors. The approach, tested on a mouse model, combined radiation with an antipsychotic drug and a statin used to lower high cholesterol levels, and it was found to extend the median survival of the mice four-fold compared to radiation alone.
Radiation therapy is part of the standard-of-care treatment regimen for glioblastoma, often helping prolong the survival of patients. However, survival times have not improved significantly over the past two decades. There have been attempts to improve the efficacy of radiotherapy through the use of pharmaceuticals; however, the treatments have been hampered by the normal tissue toxicity of the drugs, as well as their inability to penetrate the blood-brain barrier, which protects the central nervous system.
In this trial, the team in the lab of Frank Pajonk, MD, PhD, professor of radiation oncology and a member of the Jonsson Cancer Center, tested the approach using patient-derived glioblastoma lines provided by the Biospecimen and Pathology Core of the UCLA SPORE in Brain Cancer. They discovered that the antipsychotic drug quetiapine, which acts to block dopamine receptors and is able to rapidly cross the blood-brain barrier, enhanced the efficacy of radiotherapy in glioblastoma.
However, the combination of quetiapine and radiation also provoked a resistance mechanism; it induced the synthesis of cholesterol, which helps glioblastoma cells survive. The researchers used Atorvastatin (Lipitor), which is also able to cross the blood-brain barrier, to target and inhibit the cholesterol-biosynthesis pathway.
The results of the study provide evidence that using quetiapine in combination with Atorvastatin and radiation may help extend the survival for people with glioblastoma. The study authors also point out that this therapy includes FDA-approved drugs that can rapidly be translated into a clinical trial.
— Denise Heady
“Dopamine Receptor Antagonists, Radiation, and Cholesterol Biosynthesis in Mouse Models of Glioblastoma,” Journal of the National Cancer Institute, Febrary 9, 2021