Neuroactive drugs show promising anti-glioblastoma effects in preclinical trials
Researchers find that the antidepressant vortioxetine may offer new hope for glioblastoma patients by crossing the blood-brain barrier and significantly reducing tumor size in preclinical models.
A recent Nature Medicine study evaluates the potential to repurpose currently approved drugs to treat cancer and neurological disorders for their therapeutic effects against glioblastoma.
Glioblastoma is an incurable and fatal type of brain cancer, with about 50% of patients dying within twelve months of diagnosis. The life expectancy of glioblastoma patients can be extended through radiation, chemotherapy, or surgical interventions.
Many drugs that are used to treat cancer cannot cross the blood-brain barrier (BBB), thus limiting the utility of these agents in treating brain tumors like glioblastoma. Targeted therapies have been associated with limited success in the treatment of glioblastoma due to the lack of clinically predictive patient model systems, as well as the presence of treatment-resistant glioblastoma stem cells (GSCs).
In the current study, researchers used pharmacoscopy to simultaneously test the in vitro and in vivo efficacy of both neuroactive and oncology drug (ONCD) libraries against glioblastoma patient samples.
The neuroactive drug library consisted of drugs capable of crossing the BBB that are currently approved for the treatment of neurological diseases like Alzheimer’s disease, depression, and schizophrenia. Comparatively, the ONCD drug library consisted of conventional cancer treatments, such as cyclin-dependent kinase (CDK) and receptor tyrosine kinase (RTK) inhibitors.
A total of 130 different agents were used to treat tumor tissues isolated from 27 patients who recently underwent surgery at the University Hospital Zurich. Imaging techniques and computer analysis were used to identify drugs that influenced cancer cells.
Several ONCDs were capable of penetrating the BBB, which included elesclomol, osimertinib, and regorafenib.
Innovative machine learning approach: The researchers utilized the COSTAR model, analyzing over one million compounds, to predict which drugs target shared glioblastoma vulnerabilities and enhance treatment efficacy.
Fifteen NADs exhibited anti-glioblastoma activity, with vortioxetine, an antidepressant, inducing significant ex vivo efficacy in about 67% of patient samples. Other potent NADs were paroxetine, fluoxetine, and brexpiprazole.
Vortioxetine was consistently the most effective NAD in vivo, especially in combination with the current standard treatment. Furthermore, the survival benefits associated with vortioxetine treatment were significant and similar to those of alkylating agent temozolomide (TMZ).
