In a new study, researchers have found that adding a drug once commonly used to treat schizophrenia to traditional radiation therapy helped improve overall survival in glioblastoma, one of the deadliest and most difficult-to-treat brain tumors.
The findings show that a combination of radiation and the drug trifluoperazine not only targets glioblastoma cells but also helps overcome the resistance to treatment so common to this aggressive form of cancer.
The results could prove promising for patients with the disease, for whom the median survival time is only 12 to 18 months following diagnosis.
The research was conducted by a team at the UCLA Jonsson Comprehensive Cancer Center.
Radiation is an integral part of therapy for people with cancer and one of the most effective treatments. In many cases, it can help cure the disease.
But in glioblastoma, tumor cells often become resistant to radiation treatment because the radiation itself can induce “phenotype conversion,” a process that turns certain non-tumor stem cells into tumor-producing cells, causing cancer to reoccur.
The drug trifluoperazine by itself does not do much either, but we found when you combine them, they become highly efficient.
Importantly, the drug does not sensitize cells to radiation but rather prevents the occurrence of resistant glioma stem cells.
The UCLA researchers have been exploring new ways to prevent glioblastoma tumor cells from becoming resistant to radiation by adding drugs to the treatment regimen that have traditionally been used for other purposes.
To find out if there were any existing drugs that could interfere with the radiation-induced phenotype conversion, the team screened more than 83,000 compounds through the shared resources at UCLA, which provides researchers access to specialized equipment and services to help them pursue cutting-edge research.
They were able to identify nearly 300 compounds, including the dopamine receptor antagonist trifluoperazine, that had the potential to block phenotype conversion and improve the efficacy of radiation therapy.
Once trifluoperazine was identified, it was tested on mice with patient-derived orthotopic tumors.
The team found that, when used in combination with radiation, trifluoperazine successfully delayed the growth of the tumors and strongly prolonged the overall survival of the animals.
Combining radiation treatment with trifluoperazine extended survival in 100% of the mice to more than 200 days, compared to 67.7 days in the control group receiving only radiation.
The team plans to start a clinical trial this summer for people with recurrent glioblastoma to test using dopamine receptor antagonists with radiation therapy.
One author of the study is Dr. Frank Pajonk, a professor of radiation oncology.
The study is published in the Proceedings of the National Academy of Sciences.
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