Glioblastoma, an aggressive brain cancer, has a very poor prognosis. More than 95% of glioblastoma patients die within five years of diagnosis. Glioblastoma has an incidence rate of 3.19 per 100,000 persons in the United States. Glioblastoma occurs 1.6 times more often in males than females. Racial differences in diagnostics also suggest the highest risk for glioblastoma for White individuals compared to Black individuals.
Standard-of-care treatment for glioblastoma typically involves systemic chemotherapy, specifically a class of drugs known as alkylating agents. These treatments, including the chemotherapy drug temozolomide (TMZ), work by damaging the DNA in cancer cells. Alkylating chemotherapy drugs replace the hydrogen atoms on DNA with alkyl groups, leading to cross-linkages between DNA chains. Once DNA has become damaged, it can no longer replicate, and the cancer cells die without being replaced.
Several clinical challenges remain for glioblastoma, including a need to cross the blood-brain barrier, a protective layer that prevents many substances, including drugs, from entering the brain. Such challenges have resulted in minimal advancement of novel treatment options for this disease. A new study in Nature Medicine suggests that repurposing established neuroactive drugs, which can cross the blood-brain barrier, could benefit glioblastoma patients.
The researchers screened established neuroactive drugs using glioblastoma surgical specimens from 27 patients. The drugs tested included antidepressants and antipsychotics that can reach tissue in the brain. The screening evaluated 132 for anti-glioblastoma efficacy. The study identified a particular antidepressant drug, vortioxetine, as remarkably effective against glioblastoma cells in the patient tissue, highlighting its potential.
Next, the researchers used a pre-clinical mouse model to test the efficacy of a combination treatment approach by administering both vortioxetine and TMZ. Notably, vortioxetine synergized with chemotherapy, significantly prolonging survival for animals receiving the combination treatment. This synergy refers to the combined effect of the two drugs being greater than the sum of their individual effects, suggesting a potential for more effective treatment.
The study concludes that oncologists may be able to repurpose an existing antidepressant for treating glioblastoma. These findings provide a strong rationale for additional pre-clinical research to validate the anti-glioblastoma efficacy of vortioxetine as well as the synergistic nature of this antidepressant and chemotherapy approach. This work could pave the way for clinical trials to test the safety and effectiveness of this strategy in patients.
Sources: Glioblastoma, Nature Med, Nat Rev Dis Primers