UIC researchers awarded $2.67 million to develop pediatric brain tumor treatments

Researchers at the University of Illinois Chicago have been awarded a five-year, $2.67 million grant from the National Cancer Institute to develop and study novel treatments for childhood brain cancer.

Led by Tohru Yamada, associate professor in the colleges of Medicine and Engineering at UIC, the project will develop a cancer-targeting peptide that's fine-tuned to shrink brain tumors in pediatric patients.

There currently is no FDA-approved drug on the market to treat pediatric high-grade gliomas, which are tumors originating in the brain and spinal cord. These tumors are the leading cause of cancer death in all patients age 19 and younger.

Chemotherapies to treat adult gliomas include the drug Temozolomide, which works by interfering with DNA synthesis. However, its efficacy is unproven in children, due to molecular differences between child and adult tumors.

"Although they're both called brain cancer, pediatric brain cancer and adult brain cancer are not the same on the molecular level," said Yamada, who is a member of the University of Illinois Cancer Center.

Yamada's group focused on genes that can contribute to the growth of brain tumors in children. In their new project, they plan to target one of these genes and prevent its function by treating it with short strands of molecules that neutralize its activity.

To deliver these neutralizing molecules to brain tumors, they will attach them to peptides - or fragments of proteins - that can cross the blood-brain barrier. This is the layer of cells surrounding the brain that protects it from harmful substances, but it also blocks many drugs from penetrating when and where needed.

"It acts as a protective barrier that helps keep infections and many toxic components out of the brain," Yamada said. "But the blood-brain barrier is a major roadblock. Not many agents can cross it and target brain cancer."

In previous research, Yamada and colleagues identified a peptide in bacteria that could cross this barrier. They found it can cross the blood-brain barrier faster than the chemotherapy drug Temozolomide, and it stays in the brain longer.

The researchers will use the peptide as a vehicle to shuttle the tumor-neutralizing molecules into the brain via an injection into the blood. Preliminary tests have shown that the treatment kills tumor cells and prolongs lifespans in animal models of the disease.

The researchers will test the approach in different types of brain cancer that occur in different regions of the brain. They will also study the drug's potential side effects and interactions and how it's metabolized in the body.

"We think this strategy will be an important step in treating pediatric gliomas, which are currently uncurable," Yamada said.

In addition to UIC-based collaborators Konstantin Christov, associate professor of surgery, and Jing Wang, professor of math, statistics and computer science, Yamada will partner with collaborators at Phoenix Children's Hospital in Phoenix, Arizona.