A mix of 2 drugs could block the growth of glioblastoma cells, the most aggressive brain tumor, still without a cure. An Italian study conducted as part of Spoke 3 of the Mnesys project, the ‘Italian Cern’ for brain research financed by the Pnrr, opens up new therapeutic perspectives. It was discussed in Naples at the 1st National Neuroscience Forum.
“Despite the scientific progress of recent years in the characterization and classification of these brain tumors, the therapeutic ‘weapons’ available to doctors are still few and often ineffective and glioblastoma remains an incurable brain tumor today, with a survival time low median, equal to 15 months”, recalls Lorenzo Chiariotti, professor of General Pathology at the Federico II University of Naples. In a study published in September 2023 in ‘Cell Death & Disease’, scientists led by Chiariotti discovered that in more than half of the glioblastomas analyzed, the enzyme lysine methyltransferase (Setd8) is more highly expressed than in normal brain tissue. Based on this observation, “we treated glioblastoma cells with UNC0379, a specific inhibitor of Setd8 – reports the specialist – and noticed that the proliferation of malignant cells was reduced. We then managed to demonstrate that the combination of the Setd8 inhibitor with an experimental anticancer drug, adavosertib, induces the death of glioblastoma cells. The experiments were also conducted on mouse models in which glioblastoma cells were implanted in the side of the animals and the result – highlights Chiariotti – was confirmed: the UNC0379-adavosertib association blocks the growth of glioblastoma cells even in animal models“.
“And that’s not all. The chemical-physical characteristics of UNC0379 – adds the expert – suggest that the drug is able to cross the blood-brain barrier, i.e. the functional structure interposed between blood and nervous tissue, which selectively regulates the blood passage of chemicals to and from the brain, protecting the nervous system from poisoning and intoxication Studies are currently underway to demonstrate the permeability of UNC0379 across the barrier in mouse models. Formal in vivo evidence of the drug’s ability to achieve the brain – specifies Chiariotti – is a necessary condition to be able, eventually, to give the go-ahead clinical studies on humans“.
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