Research Spotlight: Praveen Raju

A Breakthrough in Delivery: Rethinking What’s Possible for DIPG

One of the greatest challenges in treating DIPG has never just been finding promising drugs, it’s also been getting them to the tumor.

Dr. Praveen Raju and his team set out to change that. With support from a ChadTough Defeat DIPG Foundation Game Changer Grant, they are advancing a new nanoparticle-based technology designed to deliver cancer drugs directly to brain tumors while sparing healthy tissue. Their findings show improved effectiveness and reduced toxicities—an important step forward in how these therapies may one day reach patients.

“We show that we can more effectively deliver lower doses of the drug directly to tumor sites in the brain, while sparing the known toxicities seen with many anti-cancer therapies,” said Praveen Raju, MD, PhD, senior author of the study, who served as Co-Director of the Children’s Brain and Spinal Tumor Center at Mount Sinai Kravis Children’s Hospital at the time of the award and now directs the Pediatric Brain Tumor Program at Rady Children’s Hospital and UC San Diego.

Turning a Barrier into an Opportunity

Most cancer drugs simply cannot reach tumors in the brain. In fact, more than 98% of small molecule drugs, and nearly all larger therapies, are blocked at the blood-brain barrier before they ever get to the tumor site.
Dr. Raju’s team approached this challenge by learning from the body itself. The immune system has a natural “homing” mechanism that directs white blood cells to sites of injury or infection. Instead of circulating randomly, these cells are guided to exactly where they are needed.

The researchers harnessed this same mechanism, also present in brain tumor blood vessels, to guide their drug-loaded nanoparticles directly to the tumor, avoiding healthy brain tissue. They also found that this targeted delivery could be further enhanced using very low doses of radiation, a standard therapy already used in treating brain tumors.

Using this approach, the team successfully delivered therapies that typically cannot cross the blood-brain barrier directly into DIPG/DMG tumors in preclinical models by using lower doses and reducing potential side effects.
This breakthrough does something incredibly important: it allows researchers to revisit treatments that once looked promising in the lab but failed in patients—not because the drugs didn’t work, but because they couldn’t be delivered effectively. 

Now, those therapies may have a second chance with this drug delivery technology which  also creates opportunities for new drug combinations that cannot be used together due to the additive side effects.
Even more exciting, Dr. Raju’s team has expanded this platform to an entirely new class of drugs known as “protein degraders,” or PROTACs, opening the door to targeting a vast number of cancer-driving proteins that were previously considered ‘undruggable’.

What Comes Next
Researchers believe this delivery platform could extend far beyond DIPG, with potential applications across other brain tumors, cancers throughout the body, and even inflammatory diseases of the central nervous system.
While additional studies are ongoing, breakthroughs like this represent meaningful progress toward better treatments and brighter futures. ChadTough Defeat DIPG is proud to have supported this work and to continue investing in the discoveries that will define what comes next.