March 24, 2026
Mayo Clinic researchers are pursuing several promising leads in the development of therapies to extend survival for children with diffuse intrinsic pontine glioma (DIPG). Although rare, DIPG has a dismal prognosis. No medications specifically targeting tumors in the pons have been approved.
"We haven't found any drug or a way to deliver any drug that extends survival. But we are hopeful of finding an efficacious therapy," says David J. Daniels M.D., Ph.D., a pediatric neurosurgeon at Mayo Clinic in Rochester, Minnesota.
The researchers hope to translate laboratory work into clinical trials focused on:
- Combining radiotherapy with an immunotoxin therapy that targets the interleukin-13 receptor subunit alpha 2 (IL-13Ra2) signaling complex.
- Using nanoparticles to deliver to tumors therapies already approved by the Food and Drug Administration (FDA).
- Delivering medications to tumors via stereotactic electroencephalography (sEEG) leads.
- Using convection-enhanced delivery that not only overcomes the blood-brain barrier but also prevents rapid clearance of drugs from the brain.
Improving drug delivery is key. "Numerous clinical trials for DIPG medications have failed — not necessarily because the wrong drugs were tested," Dr. Daniels says. "These drugs can kill tumors in a petri dish. The challenge is getting a drug to the tumor in patients and making sure it doesn't clear the brain too quickly to have the appropriate therapeutic effect."
This work investigating pharmacology and novel therapeutics for pediatric brain tumors is part of the research arm of Mayo Clinic Comprehensive Cancer Center.
Boosting radiotherapy's efficacy
Radiotherapy — the cornerstone of DIPG treatment — confers only a three-month survival benefit. But Mayo Clinic researchers have shown that efficacy can be improved with neoadjuvant and concomitant immunotherapy targeting IL-13Ra2. That receptor is upregulated in most DIPG tumors.
As described in Communications Biology, the researchers tested on laboratory models a combined treatment with radiotherapy and GB13, an IL-13Ra2-directed immunotoxin. GB13 was delivered directly to tumors in immunocompromised patient-derived orthotopic xenografts and immunocompetent genetically engineered mouse models. The researchers found clear enhancement of radiosensitization and increased tumor cell cytotoxicity in both types of models.
"Our studies clearly show that this drug works on the tumors that have this IL-13 receptor," Dr. Daniels says. "This is also the only drug we've seen that has efficacy after just one dose. Every other drug we've tested has required multiple doses."
GB13 targets a specific epitope that is expressed in the tumor but not in healthy tissue throughout the body. "That lessens the drug's toxicity," Dr. Daniels says. "This therapy definitely has merit."
Overcoming barriers to drug delivery
Mayo Clinic researchers have developed a method for encapsulating FDA-approved medications into a nanoparticle derived from pooled patient plasma.
"We have found that the particle gets selectively and heavily taken up by tumor cells. The tumors just want to eat this particle up," Dr. Daniels says. "We get more drug into the tumors with this technology. Our nanoparticle outperforms the free drug and other nanoparticle formulations."
"This is also the only drug we've seen that has efficacy after just one dose."
Another potential delivery method involves sEEG leads. These tiny filaments implanted in the brain are used to record electrical activity in people with epilepsy. "The leads essentially are hollow in the middle. They could be used to simultaneously deliver FDA-approved tumor drugs and monitor electrical activity," Dr. Daniels says.
Monitoring electrical activity in patients' brains could potentially shed light on how the brain reacts to antitumor drugs. "If electrical activity changes when these drugs are present, can we get a sense of where the drug is going?" Dr. Daniels says. He hopes to launch preclinical studies of this approach.
Another major challenge is overcoming the efflux transporters — present in the blood-brain barrier and in tumors themselves — that clear cancer medications. "We have found that clearance happens super quickly," Dr. Daniels says. "The medications interact with the tumor for only around 30 minutes. That's not long enough to make a difference."
In preclinical research, Dr. Daniels's team has developed a method of convection-enhanced delivery that brings medications directly to the brain while blocking efflux transporters. "What's surprising to us is that when we block those efflux transporters, we see a big difference in the drug residency time," Dr. Daniels says. "We actually see drug efficacy where we didn't see it before."
Finding improved treatment for DIPG requires not only research expertise but also a deep commitment of time and resources. "Clinical trials have failed partly because new therapies haven't been rigorously tested ahead of time," Dr. Daniels says. "Mayo Clinic gives researchers the time and ability to be creative. The institution values that. Our benchwork ultimately will get to clinical trials that we hope will make a difference."
For more information
Mayo Clinic Comprehensive Cancer Center. Mayo Clinic.
Rechberger JS, et al. Radiotherapy plus neoadjuvant and concomitant IL-13Ra2-directed immunotoxin therapy for diffuse intrinsic pontine glioma. Communications Biology. 2026;9:78.
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