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Hope for children with previously incurable brain cancer

Date:
April 7, 2014
Source:
University of Toronto
Summary:
Potential treatment targets for a previously incurable form of pediatric brain cancer called Diffuse Intrinsic Pontine Glioma has been revealed by scientists. The researchers believe 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," one expert noted.

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 Department of Laboratory Medicine and Pathobiology (LMP) have defined potential treatment targets for this relatively common cancer -- providing hope for future patients.

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In this groundbreaking research published in Nature Genetics, LMP Professor Cynthia Hawkins, a Scientist and Neuropathologist at The Hospital for Sick Children, along with PhD candidates Pawel Buczkowicz and Patricia Rakopoulos, identified three subgroups of DIPG, each having distinct molecular features.

"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 percent 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.

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


Story Source:

The above story is based on materials provided by University of Toronto. Note: Materials may be edited for content and length.


Journal Reference:

  1. Pawel Buczkowicz, Christine Hoeman, Patricia Rakopoulos, Sanja Pajovic, Louis Letourneau, Misko Dzamba, Andrew Morrison, Peter Lewis, Eric Bouffet, Ute Bartels, Jennifer Zuccaro, Sameer Agnihotri, Scott Ryall, Mark Barszczyk, Yevgen Chornenkyy, Mathieu Bourgey, Guillaume Bourque, Alexandre Montpetit, Francisco Cordero, Pedro Castelo-Branco, Joshua Mangerel, Uri Tabori, King Ching Ho, Annie Huang, Kathryn R Taylor, Alan Mackay, Anne E Bendel, Javad Nazarian, Jason R Fangusaro, Matthias A Karajannis, David Zagzag, Nicholas K Foreman, Andrew Donson, Julia V Hegert, Amy Smith, Jennifer Chan, Lucy Lafay-Cousin, Sandra Dunn, Juliette Hukin, Chris Dunham, Katrin Scheinemann, Jean Michaud, Shayna Zelcer, David Ramsay, Jason Cain, Cameron Brennan, Mark M Souweidane, Chris Jones, C David Allis, Michael Brudno, Oren Becher, Cynthia Hawkins. Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. Nature Genetics, 2014; DOI: 10.1038/ng.2936

Cite This Page:

University of Toronto. "Hope for children with previously incurable brain cancer." ScienceDaily. ScienceDaily, 7 April 2014. <www.sciencedaily.com/releases/2014/04/140407113353.htm>.
University of Toronto. (2014, April 7). Hope for children with previously incurable brain cancer. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2014/04/140407113353.htm
University of Toronto. "Hope for children with previously incurable brain cancer." ScienceDaily. www.sciencedaily.com/releases/2014/04/140407113353.htm (accessed November 28, 2014).

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