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Imagine the anguish of a parent whose child is diagnosed with an incurable form of childhood brain cancer. Surgery is not an option, current chemotherapy is ineffective and focal radiation only provides temporary relief.

Remarkably, researchers from the University of Toronto’s Department of Laboratory Medicine and Pathobiology (LMP) have defined potential treatment targets for this relatively common cancer – providing hope for future patients.

In this groundbreaking research published in , Dr. Cynthia Hawkins, a professor at LMP and Neuropathologist and Scientist at The Hospital for Sick Children, along with PhD candidates Pawel Buczkowicz and Patricia Rakopoulos, identified three subgroups of what are known as DIPGs (diffuse intrinisc pontine gliomas), each having distinct molecular features.

"In the past, DIPGs were considered one disease and were assumed to be similar to adult brain tumours. For this reason, the treatments that were given to adults were also given to children—but these treatments were ineffective,” said Buczkowicz. By studying the differences between these tumours, the team can now investigate potential treatments.

DIPGs are known as one of the most challenging tumours to treat because cancer cells are intimately intermingled with normal brain cells in a part of the brain that cannot be surgically resected. They are most commonly diagnosed in children between the ages of five and nine and account for 10 to 15 percent of all pediatric central nervous system tumours.

For over 25 years, there have been few advances in research. Doctors used MRI or CT scans to diagnose and study DIPGs, but the information obtained was limited. In addition, it was difficult to study these tumours because they were rarely biopsied and tissue samples were rare. Hawkins began an autopsy-based study to gain a comprehensive perspective of the disease, an approach that has paid dividends.

“I think what’s interesting about combining whole genome analysis and histopathology is that we can study the tumour at multiple levels,” said co-author Rakopoulos. “We’re able to see at the molecular level down to a single nucleotide and then we have the view from the very top. It’s important to have as many perspectives as possible.”

The team discovered that DIPGs could be more accurately classified into three subgroups: H3-K27M, Silent and MYCN. They also revealed a new recurrent activating mutation in the activin receptor ACVR1. With these breakthroughs, they can now investigate potential therapeutics that will target these subgroups.

“We’re hoping that by having a better genetic characterization of these cancers we can try to better target these tumours and provide a personalized approach to treatment," Hawkins said. "The ideal is always that we’re going to find something that will zap all of the tumour cells and we’re going to find a cure. But probably a more realistic interim goal is that we can at least slow it down.”

Phase I clinical trials for DIPG could potentially begin within a year.

Katie Babcock is a writer with the Department of Laboratory Medicine and Pathobiology in the Faculty of Medicine at the University of Toronto.