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About SickKids

June 19, 2014

Current treatments miss slowly-dividing cancer cells, risking fatal relapse of childhood brain tumour, SickKids-led study finds

TORONTO – Aggressive chemotherapy attacking rapidly-dividing cancer cells have greatly improved survival rates for the most common cancerous brain tumour in children; however, nearly 30 per cent of cases result in a fatal recurrence of the tumour. New research led by The Hospital for Sick Children (SickKids) identifies a culprit for relapse in medulloblastoma: a small group of slowly-dividing tumour cells that slide under the radar of traditional therapies. The findings suggest these cells should be a new target for treatment. The study is published in the June 19 online edition of Cancer Cell.

Current treatments for medulloblastoma, a cancer in the cerebellum, although effective in inducing remission, often leave children with significant neurological, intellectual and physical impairments due to their effects on the developing brain. No effective therapies exist for relapse.

The international research team set out to better understand how medulloblastoma tumours grow and why existing treatments fail, aiming to generate a novel approach to treatment. Using a technique called lineage tracing, they engineered coloured marks in specific tumour stem cells (marked by the stem cell gene Sox2) in mouse models. They continued to trace marks as the tumour grew or when it was subjected to treatment. Tracking the properties of cells as they grew in an actual tumour enabled the researchers to determine which cell type is most responsible for tumour growth and relapse.

They found that while traditional chemotherapy destroyed the majority of rapidly-dividing tumour cells in the mice, causing tumours to shrink, a rare population of slowly-dividing cells that had a stem cell character were left behind. These cells multiplied quietly, regenerating the rapidly-dividing cells, and gaining strength to become a more powerful version of the tumour, which is almost always fatal.  

“By dissecting the cellular determinants of tumour growth, we found that different tumour cells have very distinct properties in terms of how quickly they divide and how they respond to therapy,” says Dr. Peter Dirks, principal investigator of the study, Staff Neurosurgeon and Senior Scientist at SickKids. “Our work suggests new treatments will be required to target the slowly-dividing tumour cells that have stem cell properties and can result in tumour regrowth after apparently-successful treatment.”  

Robert Vanner, lead author of the study and a PhD student in Molecular Genetics at the University of Toronto, adds “this study highlights the power of lineage tracing to gain new insight into the biology and treatment of brain tumours.”

The researchers also showed that in human medulloblastoma, the presence of many cells that express the stem cell marker Sox2 is associated with a worse prognosis, suggesting that these cells also contribute to the risk of relapse.

Several chemotherapy drugs were tested on slowly-dividing cancer stem cells derived from human medulloblastoma tumours grown in the lab mice, and the research team was able to identify several promising options, including one existing drug, mithramycin, that halted tumour growth in the mice. Future studies would test drugs targeting this stem-cell population with eventual clinical trials.

“We predict that the most successful future medulloblastoma therapy will need to target these different cell types in the tumour,” says Dirks, who is also Principal Investigator at The Arthur and Sonia Labatt Brain Tumour Research Centre at SickKids and Professor of Neurosurgery and Molecular Genetics at the University of Toronto. “More precise targeting to each unique group of cells should lead to safer and more durable treatments, with better long-term outcomes.”

The research was funded by the Canadian Institutes of Health Research, the Ontario Institute for Cancer Research, the Canadian Cancer Society, Genome Canada and SickKids Foundation.

This work has been conducted in close collaboration with the Industry Partnerships and Commercialization Office at SickKids. Several of the reagents and human brain tumour cell cultures developed in the study are available for research collaboration.

About The Hospital for Sick Children

The Hospital for Sick Children (SickKids) is recognized as one of the world’s foremost paediatric health-care institutions and is Canada’s leading centre dedicated to advancing children’s health through the integration of patient care, research and education. Founded in 1875 and affiliated with the University of Toronto, SickKids is one of Canada’s most research-intensive hospitals and has generated discoveries that have helped children globally.  Its mission is to provide the best in complex and specialized family-centred care; pioneer scientific and clinical advancements; share expertise; foster an academic environment that nurtures health-care professionals; and champion an accessible, comprehensive and sustainable child health system. SickKids is proud of its vision for Healthier Children. A Better World. For more information, please visit www.sickkids.ca.

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For more information, please contact:


Suzanne Gold
The Hospital for Sick Children
416-813-7654, ext. 202059
suzanne.gold@sickkids.ca     

Matet Nebres
The Hospital for Sick Children
416-813-6380
matet.nebres@sickkids.ca