Rare but fatal pediatric brain tumor can be stopped with a new molecule (2020)

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

New research reveals a molecule that successfully stops DIPG – a deadly pediatric brain tumor.

Diffuse intrinsic pontin glioma (DIPG) is a pediatric brain tumor that primarily affects children under the age of 10.

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

DIPGs are extremely aggressive and difficult to do to treat, so the diagnosis with the tumor usually leads to death within a year.

However, new research offers hope for the treatment of DIPG. Scientists from Northwestern University in Evanston, IL, may have found a molecule that could stop the tumor from developing. The team was led by Ali Shilatifard, Robert Francis Furchgott Professor of Biochemistry and Pediatrics, and Chair of Biochemistry and Molecular Genetics at Northberg University Feinberg School of Medicine.

The new findings – published in the magazine Nature medicine – builds on the research Shilatifard and colleagues have done in the past. Shilatifard and his team identified the way in 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 – uses this knowledge to test the effects of pharmacological therapy on DIPG in mice.

The latter study inhibited the previously identified genetic pathway and successfully extended the life of the mice by 20 days. The drug was administered through the belly of the mice, but in this latest research, the team was investigating whether injecting the cells into the brain stem of the mice would have more robust effects.

BET bromodomain inhibitors stop tumor growth

The scientists collected tumor cell lines from an untreated patient and injected them into the brain stem of a mouse, where they grew into a tumor. The scientists then treated the mouse with a BET bromodomain inhibitor and continued to monitor the tumor clinically.

The BET bromodomain inhibitor has been used with care in several cancer models.

In this study, bromodomain proteins could no longer bind to the histone H3K27M by using the inhibitor – 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. That successfully ended tumor growth.

The study’s first author, Andrea Piunti – a postdoctoral fellow at the Shilatifard Biochemistry and Molecular Genetics Laboratory at Northwest University Feinberg School of Medicine – suggests that BET inhibitors should next be tested in a pediatric study to treat DIPG, especially since the drugs are already tested for pediatric leukemia.

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

Ali Shilatifard, older author

The lead author also notes that the currently available radiation therapy is ineffective in treating DIPG; It only adds a few months to patient survival.

Shilatifard comments on the importance of Northwestern University to make this research possible:

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

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Christina Cherry
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