Diffuse midline gliomas (DMGs) are among the most aggressive pediatric brain tumors—and they’re notoriously difficult to treat. But thanks to new research led by Dr. Jessica Tsai at Children’s Hospital Los Angeles, scientists are exploring a way to “switch off” the cancer itself—right at the source.
What’s Being Targeted? FOXR2
At the heart of this breakthrough is a gene called FOXR2. This gene normally stays off in healthy brain tissue—but in DMG, it gets mistakenly turned on, driving the growth of cancer cells.
Dr. Tsai’s team discovered that a small upstream section of DNA—called Exon -3—acts like a light switch for FOXR2. If you can block this section, you can turn FOXR2 off, and in turn, stop the cancer cells from growing.
“We’ve shown in many ways that if you block this region, not only do you turn off FOXR2—you actually kill the cancer cells that depend on it,” Dr. Tsai explained.
Why This Is a Game-Changer
FOXR2 isn’t active in normal brain tissue—only in the cancer—making it an ideal target. That means treatments that block FOXR2 could come with fewer side effects than traditional chemotherapy or radiation.
Delivering the Treatment: Tiny RNA Packages
A major challenge in treating brain tumors is the blood-brain barrier, which blocks many medications from reaching the tumor. To solve this, Dr. Tsai’s lab is using lipid nanoparticles—tiny “cars” made of fat that can cross this barrier.
Inside those nanoparticles? Small interfering RNAs (siRNAs)—tiny bits of genetic material designed to block Exon -3 and shut down FOXR2.
“You can put things in the nanoparticle—like siRNAs—and send it straight into the tumor.”
What’s Happening Now?
- In the lab: The team is optimizing dosage and timing—figuring out exactly how much of the treatment is needed and how effectively it kills DMG cells.
- In animals: They’ve created mouse models of DMG using real patient-derived tumor cells and are preparing to test the nanoparticles in vivo.
- Adding antibodies: The team is engineering the surface of the nanoparticles with antibodies to help them find and stick to the tumor cells more effectively.
What’s Next?
This project has multiple exciting directions:
- Delivery methods: Options like IV injections or direct infusion into the brain are being explored.
- New cargo types: They’re testing other gene-silencing tools like antisense oligonucleotides and even CRISPR to find the most effective “cargo” to load inside the nanoparticles.
- Fast-track to translation: If the nanoparticles prove safe and effective in animal models, Dr. Tsai believes this could move into human trials quickly.
Why It Matters
This research is a perfect example of what happens when bold ideas meet real funding. By combining genetics, nanotechnology, and targeted delivery, Dr. Tsai’s team is pioneering a treatment that doesn’t just fight cancer—it switches it off.
“It’s only because of your support that this is even possible,” said Dr. Tsai. “And we’re incredibly grateful.”