Advances in Glioma Treatment

Glioma research, including for usually fatal glioblastoma, is evolving with innovative drugs and advanced technology, offering new hope against these aggressive brain cancers.

Last year, the US Food and Drug Administration (FDA) approved the first treatment for a devastating brain cancer that primarily strikes children. Diffuse midline glioma (DMG), a type of glioma, so named because it spreads in the central structure of the brain, is almost universally fatal because it is a highly aggressive tumor that burrows into the brain stem and spinal cord areas controlling vital functions, making surgical removal impossible. 

The new drug, called dordavipron, has a two-pronged effect. It binds to a protein within tumor cells, eventually killing them, and it blocks signals that DMG cancer cells need to survive. Though the clinical trial results were modest—only 10 of the 50 patients responded to dordavipron—it nonetheless offers the first glimmer of hope for patients diagnosed with this incurable condition.

Leaders driving advances in glioma treatment

There are other positive developments in the glioma research. Agora Open Science Trust, which owns M4K Pharma, a virtual biotech company focused on developing affordable therapies for underserved pediatric conditions, announced in December a long-awaited lead candidate for the treatment of Diffuse Intrinsic Pontine Glioma (DIPG), a specific type of DMG located in the brain stem. The drug, M4K2009, was selected from a pool of several hundred compounds after demonstrating excellent potency, selectivity, brain penetration, and tolerability in preclinical models. (Charles River is a longtime partner of M4K, which operates under an unusual business model that pursues cures through totally open science.)

There are other encouraging research signs as well for glioma patients. Last year, scientists at the Wertheim UF Scripps Institute received approval from the FDA to move its first-line treatment for glioblastoma to early-phase clinical trials. Glioblastomas attack the brain’s cerebrum and are primarily seen in adults. The experimental medication, called MT-125, inhibits cancer metastasis by blocking myosin motors, proteins that drive cell division and migration. In animal studies, MT-125 rendered previously radiation-resistant malignant cells responsive to treatment. It also blocked the tumor cells’ ability to squeeze and change shape, preventing them from proliferating and invading other parts of the brain. Animal studies also found that MT-125 works effectively in combination with other chemo drugs, leading to periods of disease-free state that haven’t been observed in mouse models before.

Modifi Biosciences, a spinout company launched by the Yale School of Medicine, has also developed a treatment for glioblastoma that targets only the DNA of malignant cells while sparing healthy ones, halting their replication. Merck acquired Modifi two years ago and is hoping to move the drug KL-50 into clinical trials this year or next.

Better animal and in vitro models for glioblastoma research

One reason brain researchers are finally making inroads after years of drug failures is that the in vivo and in vitro models and technologies being used today are more effectively identifying and derisking candidates early on. 

They are also finding effective ways of crossing the blood-brain barrier (BBB), the central nervous system’s protective shield against the entry of blood-borne substances. Due to the BBB, roughly 98 percent of the small molecule drugs and all macromolecular therapeutics can’t access the brain. Fortunately, new tools and methods of drug delivery, ranging from intranasal administration and intracranial implantation to membrane coating and disruption of the BBB, are being developed to overcome this challenge.

Establishing a glioma rat model

For instance, researchers at Charles River have been using magnetic resonance imaging (MRI) to help establish a glioma rat model, whereby tumor cells are transplanted into the brain. “We can use MRI to image glioblastoma development over time,” said Riikka Immonen, a Senior Scientist at Charles River. She added that the main readouts of the study so far have been related to the permeability of the blood-brain barrier.”

The Charles River study, conducted in a highly immunodeficient rat model called SRG, used MRI to monitor tumor volume and structure, tumor vascularization, cerebral blood flow, and the extent and time course of BBB leakage. Contrast-enhanced imaging can reveal newly formed, leaky vessels, and blocking neovascularization is a key treatment strategy for gliomas. A poster on this work will be presented at the April 2026 annual meeting of the American Association for Cancer Research.

“The MRI is essential for tracking tumor growth and treatment responses, but we also use it for screening the tumors to optimize the timing for treatment, and what the baseline is for that,” says Immonen. “By applying translational in vivo imaging techniques, we can study orthotopic tumor progression and, together with the animal disease models, gain a detailed understanding of disease progression and improved treatment intervention design.”

Advanced in vitro models driving glioblastoma treatment

There are also in vitro models being used to study glioblastoma and to accelerate the development of candidate drugs. 2D and 3D glioma cell culture systems are being used to create biomimetic platforms. Researchers are turning to microphysiological systems, including brain organoids and spheroids, to study glioblastoma. Julia Schueler, Charles River’s therapeutic area lead for oncology, said their library includes 30 adult and nearly 100 pediatric patient-derived xenograft (PDX) glioblastoma models.

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The future is bright for glioma patients

Schueler said the future for patients with these deadly brain tumors is getting brighter every year. “Beyond the tremendous meaning for patients suffering from this disease, these studies showcase how a thorough preclinical development pipeline is enabling scientists to identify innovative compounds for diseases that were known to be nearly incurable for the last few decades. That’s real progress.”