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BRain tumors are among the most common – and deadliest – cancers in children. A new article, published Wednesday in the journal Cell, explores the intricacies of how brain cancer works in children and offers tantalizing clues as to how they can be treated.
A consortium of researchers explored the molecular details of 218 pediatric brain tumors, analyzing the genes, proteins and RNA transcription that allow these cancers to proliferate. This analysis, which identified a number of unique proteins created by different types of brain tumors, allowed researchers to make connections between the presence of certain proteins and a patient’s prognosis.
“This groundbreaking study takes pediatric brain tumors on a new level,” said Sriram Venneti, a neuropathologist who studies brain tumors at the University of Michigan. He did not participate in the study.
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The work, he said, “deepens our understanding of these difficult-to-treat childhood brain tumors” and helps unravel some of the complex biology that drives their growth.
Pediatric cancers are generally poorly studied, and most treatments for brain tumors in children are based on what has worked in adults. Still, brain tumors in children have fewer mutations than in adults, said Pei Wang, professor of genomics at Icahn School of Medicine at Mount Sinai who led the study. This means that therapies that target mutations found in adult cancers are not necessarily applicable in children.
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Wang’s team chose to study the functional molecular biology of low-mutation tumors because they offered a greater likelihood of finding proteomic similarities between different types of brain cancer. The idea, she said, is that establishing these links between types of brain cancer in children could help inform treatment choices.
The researchers probed the tumor samples, from seven different types of pediatric brain cancer, and some striking similarities stood out.
For example, the team identified two distinct subgroups of pediatric craniopharyngioma, a cancer that is particularly difficult to treat. One of the subgroups of these brain tumors was remarkably similar to a completely different type of brain tumor: a low-grade glioma with a BRAF mutation (V600E). This suggests that chemotherapy drugs already used successfully to treat these particular low-grade gliomas may help with some craniopharyngiomas, Wang said. The study prompted researchers to test a class of drugs called MEK / MAPK inhibitors which are typically used to treat low-grade gliomas in pediatric craniopharyngioma clinical trials.
“This is good news for pediatric patients who are in desperate need of treatment and an incentive to develop pharmaceutical drugs as it increases the market for their drugs,” said Erwin Van Meir, professor of neurosurgery at the University of London. ‘Alabama to Birmingham. He did not participate in the study.
Another interesting finding: When another type of brain tumor, high-grade glioma, carries a genetic mutation called H3K27M, the malignant cells tend to be extremely aggressive and children with this mutation usually don’t live long. Among children with high-grade gliomas who do not have the mutation, it is more difficult to know if their cancer will be particularly malignant. In these unmutated gliomas, an excess of two proteins – called IDH1 and IDH2 – suggests whether the cancer will be aggressive.
The researchers also found that the initial tumors in children looked drastically different from recurrent tumors – suggesting that an entirely new treatment method would be needed for them. Immune markers inside pediatric brain tumors also suggest that patients could immediately benefit from immunotherapies, which are not widely used in pediatric brain tumors.
“It was a discovery study, but we need clinical trials to validate most of the hypotheses that we have now generated,” Wang said. “This is all very exciting and very promising, however.
Wang said she plans to expand this proteogenomic study to young adults because clinicians are unsure whether it is better to treat them like children or adults. She also wants to better understand why tumors develop resistance to drugs, as it is difficult to chart new treatment paths when brain tumors adapt and change.
“Overall, this study is great news for children with brain tumors and their families,” said Van Meir of the University of Alabama. “Some of the results are immediately applicable in the clinic, and others reveal new directions for the future development of therapy.”
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