For glioma patients, mutated gene may open door to new treatment options

This image shows blood vessels and nuclei and depicts the blood-brain barrier

A mutated gene affects the growth of brain tumor cells in young adults, suggesting they are highly sensitive to a new treatment strategy, University of Michigan Roger Cancer Center has found

The protein-coding gene ATRX is mutated in more than half of young patients with high-grade gliomas, most commonly adolescents and adults under the age of 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 Castro-Lowenstein's 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, which only about 5 percent of drugs 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 an arm to the current trial to capture this population because we believe this is the population that will respond best to the drug

The success of this study, Koschmann said, lies in his collaboration with other researchers

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

Paper citations:

“ATRX loss in glioma results in dysregulation of cell-cycle phase transition and ATM inhibitor radio-sensitization,”Cell Reports.
DOI: 10.
1016/j.
celrep.
2021.
110216