Researchers may have found a molecule that inhibits the growth of a rare but fatal tumor that occurs in children, called diffuse intrinsic pontine glioma.

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New research uncovers a molecule that successfully halts DIPG – a fatal pediatric brain tumor.

Diffuse intrinsic pontine glioma (DIPG) is a pediatric brain tumor that mainly affects children under 10 years of age.

Approximately 300 children – usually between 5 and 9 years old – are diagnosed with DIPG every year. DIPGs are located in the brain’s pons – a brain region that controls many of the body’s vital functions, including breathing and heart rate.

DIPGs are extremely aggressive and difficult to treat, so being diagnosed with the tumor typically results in death within a year.

New research, however, offers hope for treating DIPG. Scientists from Northwestern University in Evanston, IL, may have found a molecule that could stop the development of the tumor. The team was led by Ali Shilatifard, Robert Francis Furchgott professor of biochemistry and pediatrics, and chair of biochemistry and molecular genetics at Northwestern University’s Feinberg School of Medicine.

The new findings – published in the journal Nature Medicine – build on research that Shilatifard and colleagues have carried out in the past. Shilatifard and his team identified the pathway through which a genetic mutation causes cancer in a study published in the magazine Science, and a follow-up study – conducted in collaboration with Rintaro Hashizume and his team – used this knowledge to test the effects of pharmacological therapy on DIPG in mice.

The latter study inhibited the previously identified genetic pathway and successfully prolonged the life of mice by 20 days. The drug was administered through the mice’s abdomen, but in this latest research, the team set out to investigate whether injecting the cells into the mice’s brainstem would have more robust effects.

The scientists sampled tumor cell lines from an untreated patient and injected them into a mouse’s brainstem, where it grew into a tumor. Subsequently, the scientists treated the mouse with a BET bromodomain inhibitor and went on to clinically monitor the tumor.

The BET bromodomain inhibitor has proven efficacious in several cancer models before.

In this study, by using the inhibitor, bromodomain proteins could no longer bind to the histone H3K27M – a mutant protein found in 80 percent of DIPG tumors. BET inhibitors stopped the proliferation of tumor cells, and forced them to differentiate into other cells instead. This successfully stopped tumor growth.

The study’s first author, Andrea Piunti – a postdoctoral fellow in Shilatifard’s laboratory in biochemistry and molecular genetics at Northwestern University Feinberg School of Medicine – suggests that BET inhibitors should next be tested in a pediatric trial to treat DIPG, especially since the drugs are already being tested for pediatric leukemia.

To the best of our knowledge, this is the most effective molecule so far in treating this tumor. Every other therapy that has been tried so far has failed.”

Ali Shilatifard, senior author

The senior author also notes that the currently available radiation therapy is ineffective in treating DIPG; it only adds a few months to the patients’ survival.

Shilatifard comments on the importance of Northwestern University for making this research possible:

“This work could not have been done anywhere in the world except Northwestern Medicine, because of all the scientists and physicians who have been recruited here during the past five years and how they work together to link basic scientific research to the clinic,” Shilatifard says. “This discovery is the perfect example of how we take basic science discoveries and translate them to cure diseases at Northwestern Medicine.”

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