Facebook Pixel Code
About Sickkids
About SickKids

June 4, 2009

Cancer stem cell studies could open the door to personalized, targeted treatments for brain cancers

Researchers develop new technique that maintains cancer stem cell “purity,” provide insight into targeting cells for future therapies

(Toronto) – Scientists in Toronto and in the United Kingdom have developed a new technique to efficiently grow cancer stem cells in the lab. This finding not only provides insight into how malignant brain tumours are formed, it is also a significant step forward in the quest to develop individualized therapy for patients with brain cancer. The research will be published in the June 4th advance online edition of the journal Cell Stem Cell.

The research team, comprised of scientists at The Hospital for Sick Children (SickKids), the University of Toronto and the University of Cambridge, studied glioma neural stem (GNS) cells, which form glioblastomas, the most common and aggressive types of adult brain cancer. The scientists obtained tissue samples from gliomas donated by recently-diagnosed patients. Using these samples, they developed a technique that enables cancer stem cells to grow in cultures, while maintaining their “purity” (preserving the characteristics of the stem cells and preventing them from mutating as they grow).

The problem with current techniques is that the cancer stem cells, which are considered the key cells driving cancer's growth, would not maintain their characteristics as they grew in the lab. As a result it was difficult to develop treatments to target these cells.

“We needed to create the right conditions and the right environment for stem cells to gain their footing and grow,” says the study’s principal investigator, Dr. Peter Dirks, a SickKids Neurosurgeon and Scientist and Associate Professor in the Department of Surgery at the University of Toronto.

The researchers used an adherent cell culture technique. This involves taking stem cells from the original tumour and growing them in a single layer on a surface coated with laminin. This sticky protein is found in the body and forms an adherent substrate, or the substance on which an enzyme acts. Previous techniques did not use a sticky surface. It appears this was a major factor in preserving the purity of the stem cells and allowing the cell culture to grow and recreate the patient’s specific tumour. With the new method, the tumour grown in the lab was a close match to the patient’s original tumour, allowing the scientists to study the cells as they evolved in real time.

This new method has significantly improved the efficiency of growing – and working with – these stem cells, according to Dirks. Previously, only 30 per cent of the cells would maintain their purity in a culture. By ensuring the proper conditions to preserve the characteristics of stem cells, the scientists are now able to grow the cells efficiently over 90 per cent of the time. “It’s like having the right set of cleats on the soccer pitch – you can run much faster if you have the right traction on the field,” says Dirks.

Armed with this new technique, the researchers hope to eventually test the effectiveness of drugs on a specific patient’s stem cell culture. To speed up the process, they plan to use medications that are already on the market for other conditions, testing for previously unknown anti-cancer effects. Once an effective treatment is found for the patient’s tumour in the lab, this “personalized” therapy could be brought back to that same patient.

“The increased efficiency in developing these stem cell lines gives us the opportunity to test targeted therapies on each patient’s individual tumour and hopefully feed the treatment back to the patient within a few months of diagnosis. This is the Holy Grail,” says Dirks, adding that it would take several years for scientists to reach the point of creating individualized treatment on a patient-by-patient basis. The new research is the first step in the process.

In the meantime, this technique could also open the door to research into other types of brain tumours, allowing for more definitive exploration of the mechanisms driving the growth of cancer stem cells, Dirks says.

In another new development in brain cancer research, a separate study published June 1st in the journal Cancer Research showed that mouse models of medulloblastomas (another type of brain tumour commonly found in children) also contain small numbers of cancer stem cells that drive tumor growth. This study, by the Dirks lab at SickKids, shows how closely these tumours arising in mice parallel the human disease.

“We now know which cell to target to develop better cancer therapies,” says Ryan Ward, a University of Toronto PhD student and lead author of the study. “We can now also more carefully probe how cancer might emerge from the normal stem cells that reside in the brain.”

The studies were supported by the Canadian Cancer Society Research Institute, Genome Canada and the Ontario Genomics Institute, Canadian Institutes of Health Research, the Ontario Institute for Cancer Research, Canada’s Stem Cell Network, Jessica’s Footprint and SickKids Foundation. The Cancer Research study was also supported by b.r.a.i.n.child.

The Hospital for Sick Children (SickKids), affiliated with the University of Toronto, is Canada’s most research-intensive hospital and the largest centre dedicated to improving children’s health in the country. As innovators in child health, SickKids improves the health of children by integrating care, research and teaching. Our mission is to provide the best in complex and specialized care by creating scientific and clinical advancements, sharing our knowledge and expertise and championing the development of an accessible, comprehensive and sustainable child health system. For more information, please visit www.sickkids.ca. SickKids is committed to healthier children for a better world.

For more information, please contact:

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

Suzanne Gold
The Hospital for Sick Children
Phone: 416-813-7654 ext. 2059
email: suzanne.gold@sickkids.ca