Researchers have identified a key molecule which, by targeting only cancer cells, could revolutionize the treatment of glioblastoma, a very aggressive brain tumor.
- Selectively toxic to tumor cells, the molecule called gliocidin blocks the enzyme IMPDH2, essential for the synthesis of nucleotides, thus causing the death of cancer cells.
- In tests in mice, gliocidin crossed the blood-brain barrier, slowed tumor growth and prolonged survival, especially in combination with temozolomide chemotherapy.
- Without notable side effects, this treatment could pave the way for new clinical trials and improve the outlook for patients.
With approximately 2,400 new cases diagnosed each year in France, glioblastoma is the most common brain cancer in adults. It is also one of the deadliest. Despite current therapies, patient survival rates remain desperately low. Several obstacles make this disease difficult to treat: a great diversity of cells within tumors, few exploitable genetic targets, a tumor environment weakening immune defenses, and the blood-brain barrier which limits access of drugs to the brain.
Gliocidin to destroy tumor cells
However, a team of researchers from the Memorial Sloan-Kettering Cancer Center in New York has just made a discovery that could be a game-changer: a molecule, gliocidin, capable of selectively destroying glioblastoma cells while sparing healthy cells. A treatment that could revolutionize the management of this extremely aggressive brain tumor.
As part of their work, published in the journal Naturescientists screened more than 200,000 chemical compounds to identify molecules capable of killing glioblastoma cells. Gliocidin clearly stood out for its targeted toxic action, according to a press release. By delving deeper into its mechanism of action, the team discovered that gliocidin acts as a “pro-drug” : once activated in the body, it indirectly blocks the IMPDH2 enzyme, essential for the synthesis of guanine nucleotides. This inhibition causes stress at the level of DNA replication, leading to the death of tumor cells.
Promising results in mice
Tests on mice showed that gliocidin effectively crosses the blood-brain barrier, slows tumor growth and prolongs animal survival. Combined with temozolomide chemotherapy, which stimulates gliocidin activation, the treatment further improved outcomes. Note that the treated rodents showed no notable side effects: they retained their weight, their organs were healthy and their immune system intact.
These results make gliocidin a promising candidate for future clinical trials. By addressing the specific molecular weaknesses of glioblastoma while minimizing side effects, this “pro-drug” could significantly improve the outlook for patients with this tumor.
