Hope for children with Diffuse Intrinsic Pontine Glioma

7/4/2014

Hopeful news for children with brain cancer, where surgery is not an option, current chemotherapy is ineffective and relief from focal radiation is temporary.

Researchers have defined potential treatment targets for this relatively common cancer, providing hope for future patients. They identified three subgroups of Diffuse Intrinsic Pontine Glioma (DIPG), each having distinct molecular features.

This groundbreaking research was led by the University of Toronto's Department of Laboratory Medicine and Pathobiology (LMP) Professor Cynthia Hawkins, a Scientist and Neuropathologist at The Hospital for Sick Children, along with PhD candidates Pawel Buczkowicz and Patricia Rakopoulos, and has been published in Nature Genetics.

Current approach for Diffuse Intrinsic Pontine Glioma

"In the past, DIPGs were considered one disease and were assumed to be similar to adult brain tumors. 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 tumors, the team can now investigate potential treatments.

DIPGs are known as one of the most challenging tumors 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 5 and 9 and account for 10% to 15% of all pediatric central nervous system tumors.

Previously, 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 tumors because they were rarely biopsied and tissue samples were rare. Prof. Hawkins began an autopsy-based study to gain a comprehensive molecular and histological perspective of the disease.

New promise in genetic analysis

"I think what's interesting about combining whole genome analysis and histopathology is that we can study the tumor 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.

Prof. Hawkins believes that this discovery could lead to better treatment. "We're hoping that by having a better genetic characterization of these cancers we can try to better target these tumors and provide a personalized approach to treatment. The ideal is always that we're going to find something that will zap all of the tumor 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 1 clinical trials for DIPG could potentially begin within a year.

 

Source: Science Daily: http://www.sciencedaily.com/releases/2014/04/140407113353.htm

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