Cell Research: A new strategy for gene mutation therapy in glioma

Glioma is a common tumor that originates in the brain

Their findings were published in the journal Cell Reports under the title " ATRX loss in glioma results in dysregulation of cell-cycle phase transition and ATM inhibitor radio-sensitization

The protein-coding gene ATRX is mutated in more than half of young adult glioma patients, most commonly adolescents and adults under 40

The study gave Koschmann and his team a deeper understanding of how the atrx mutant works in glioma cells and how it interacts with a class of drugs known as ATM inhibitors

Radiation normally stops cells from cycling and dividing, and healthy cells and glioma cells use this time to repair damaged DNA to keep cells alive

Armed with this knowledge, the team studied how radiosensitizers (drugs taken with radiation) interact with atrx mutant cells and target this unique biological property

In a previous study, Koschmann and his colleagues in the Castro-Lowenstein lab found that radiation therapy was an effective treatment for patients with gliomas with mutations in the ATRX gene

"We were inundated with this data," Koschmann said

Unlike other types of cancer in other parts of the body, the difficulty in treating brain tumors lies in the blood-brain barrier, through which only about 5 percent of drugs can cross, Koschmann explained

While the study was conducted with mice in the lab, the team hopes the findings will have implications outside the lab as well

"For patients with gliomas with this mutation, this class of drugs would not be considered

The team is currently in communication with the manufacturers of the ATM inhibitors used in this study to understand how these findings can best be incorporated into clinical trials

Koschmann explained: "Our hope is that the trial sponsor will either start a new trial or add a branch to the current trial to capture this population because we believe this is the population that will respond best to this drug.

Koschmann added that the success of the study lies in the collaboration between him and his colleagues

"I'm a pediatric neuro-oncologist, but we have collaborators from neurosurgery, radiation oncology, pathology and bioinformatics," he said