Ethan White first noticed something was wrong at drum practice. A snare drummer in the University of Michigan marching band, he suddenly could no longer feel the muscles in his right hand gripping the drumstick. Weeks earlier, he had marched on the field as the Wolverines won the 2023 national football championship.
Then Ethan tripped while walking up stairs. The university’s health service suggested he see a neurologist. In March 2024, Ethan, then 20, was diagnosed with diffuse midline glioma, or D.M.G., an aggressive type of brain tumor that most commonly affects children and adolescents but can also occur in adults.
D.M.G. is the deadliest pediatric cancer. Children diagnosed with it were historically expected to survive about a year. For decades, they faced the same limited treatments and the same dismal outcomes: Radiation could temporarily slow the tumor and improve symptoms like weakness and double vision. But children inevitably died of the cancer soon after.
In the last several years, though, researchers have made significant progress in understanding D.M.G., identifying a genetic mutation underlying many cases and experimenting with therapies that targeted its effects. These treatments are far from a cure. But they appear to slow the disease in some cases, with a handful of patients living for several years.
“For the first time, we don’t get zero survival,” said Dr. Sabine Mueller, director of the Pediatric Brain Tumor Center at the University of California, San Francisco.
For scientists, it’s a cause for hope. But “it’s hard to feel hope when it’s your kid,” said Jenn Janosko, whose five-year-old daughter, Izzy Cashion, was diagnosed with D.M.G. last year. Izzy is currently in a clinical trial for CAR T-cell therapy, in which a patient’s immune cells are engineered to fight off cancer. Before her daughter’s diagnosis, Ms. Janosko worked as a pediatric oncology nurse and occasionally cared for children with D.M.G. “You knew it was a death sentence,” she said.
A ‘Big Black Box’
D.M.G. — a term sometimes used interchangeably with diffuse intrinsic pontine glioma, or D.I.P.G., a common subtype — typically strikes children between ages 5 to 15. There are about 500 new cases nationwide each year.
The first signs are often double vision, one-sided weakness or facial drooping, sometimes with headaches or vomiting. Typically, within a year of diagnosis, patients start to lose motor function and develop speech and swallowing issues. Near the end of life, they become unable to move much or communicate, and have difficulty breathing, said Dr. Michelle Monje, a professor of pediatric neuro-oncology at Stanford University.
“Kids remain pretty alert and aware of everything happening,” she said. “It’s a horrific disease.”
In the early 2000s, when Dr. Monje first treated a patient with this cancer, “it was just this big black box,” she said, impossible to remove surgically and very risky to biopsy.
Starting in the 2010s, doctors figured out how to biopsy the tumors more safely. Using cell lines from patient autopsies, Dr. Monje and other researchers learned how and where the tumors originated. And in 2012, scientists announced the discovery of a mutation present in a majority of these cancers — a major breakthrough.
That mutation interferes with a histone, a protein around which DNA is tightly wrapped inside cells, like thread around a spool, said Dr. Sriram Venneti, a neuropathologist at the University of Michigan. If that spool breaks, “the way that the DNA opens or closes for genes to be turned off or turned on gets messed up,” he said. In D.M.G., the cells get stuck in a state that promotes cancer.
As Dr. Venneti tried to figure out what might reverse the mutation, scientists elsewhere were testing a treatment called ONC201 in adults with glioblastomas, another deadly brain cancer. Though the drug failed overall in those patients, it turned out that one who had a good response had the histone mutation.
Dr. Carl Koschmann, a pediatric neuro-oncologist at the University of Michigan, and others worked with the drug’s maker, now called Jazz Pharmaceuticals, to test whether it might work for children with D.M.G.
A review of early trials found that patients with the mutation who were treated with ONC201 after initial radiation had a median survival of almost 22 months — nearly double what was typical. Researchers showed that the drug worked primarily by altering the tumor cell’s metabolism to fix the broken “spool.”
Lisa Ward’s son Jace, who was diagnosed with D.M.G. at age 20 in 2019, took the drug for 17 months. During that time, he was able to play basketball, go to school and watch sports with friends. He never spent a night in the hospital. Jace died in 2021.
“What every parent wants, short of a cure,” Ms. Ward said, “is to have the longest progression free survival, the longest time where the tumor doesn’t grow and there’s great quality of life.”
When Ethan, the University of Michigan drummer, was diagnosed, his parents, Michelle Sherman and Eric White, wanted that for him, too. But because ONC201 was only available in the United States through a clinical trial, which meant he might get a placebo, Ethan’s father began traveling to Germany every three months to buy a locally sourced version of the drug. A 90-day supply cost $18,000. Ethan received two other medicines off label, which together seemed to keep his tumor stable.
He continued living on campus, working toward his psychology degree. He went skiing and joined Dr. Koschmann’s Friday-night rock climbing group.
In summer 2025, the Food and Drug Administration approved ONC201, known as dordaviprone, for recurrent D.M.G. The approval is conditional upon an ongoing trial, but it marked the first drug ever approved for this cancer.
“It’s pretty emotional for families and for physicians,” Dr. Koschmann said.
Still, the drug doesn’t work for everyone and isn’t a cure. “This is not the home run for D.M.G.,” Dr. Koschmann said. “It is a strong base hit.”
Other experimental therapies have shown similar promise. Dr. Monje and colleagues at Stanford showed that CAR T-cell therapy could cure D.M.G. in mice and started one of the first human trials in 2020. “We saw some kids go from wheelchair-bound to walking in a number of weeks,” Dr. Monje said. One outlier patient, diagnosed in high school, remains tumor-free more than five years later. Other trials of CAR T-cell therapies are now underway.
Researchers have also showed that another immunotherapy called an oncolytic virus, which splits apart cancer cells to expose more of them to the immune system, could prolong life. One patient remained free of tumor progression for more than three years. And scientists now know how D.M.G. cells integrate into healthy neural circuits to grow and evade treatment. That is enabling researchers to begin testing existing drugs — for example, certain anti-seizure medicines — to disrupt those connections, Dr. Monje said.
But these therapies are still years away from becoming standard care — if they prove successful. And to cure D.M.G., experts believe the treatments will need to be leveraged in combination, the way doctors did for childhood leukemia and neuroblastoma, starting with one treatment that prolonged life and stacking on others to ultimately cure patients.
“We think we’re hopefully in shooting distance of that in the coming decade,” Dr. Koschmann said.
Figuring out how best to combine and sequence those drugs will require costly clinical trials. The National Institutes of Health have supported much of the research on D.M.G., but prospects have dimmed with cuts to the agency and fewer grant awards.
The lack of investment is galling to parents. A few hundred children a year “may not seem like a lot,” Ms. Janosko said. But those families “are guaranteed a horrible death,” she added.
In April 2025, an M.R.I. showed that Ethan’s tumor had grown. After an experimental treatment failed, he began having new symptoms, including blurred vision and weakness.
He received more radiation and joined a trial for a newer version of dordaviprone.
Ethan never regained full function. He was bent on finishing his degree, though, and in December, his father wheeled him across the graduation stage in cap and gown.
In the spring, Ethan’s family traveled to Hawaii, where he was able to take an adaptive surfing lesson.
But in May, another M.R.I. showed the tumor was growing again. Within weeks, Ethan lost his ability to speak and walk. He was put on hospice at home. He could only nod yes or no to his parents’ questions, but he remained playful with his expressions. He could still enjoy his favorite foods — bagels with lox and cream cheese, a Ben and Jerry’s ice cream bar — and visits with friends, but he often felt sad when they left.
Before his recent decline, Ethan and his mother had picked out a chocolate Labrador puppy, which Ethan named Moose. “When Ethan is not here anymore, that dog is going to mean a lot,” Ms. Sherman said.
His tumor was still growing unchecked. The advances in treating cancers like his “can’t come soon enough,” she said.
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