"The discovery of a cancer stem cell for brain tumours means that only a small number of cells in a brain tumour have the ability to drive tumour growth. Many current cancer therapies may fail because they do not kill the cancer-sustaining stem cells. We now have to work on designing therapies that will attack these stem cells," said Dr. Peter Dirks, an HSC neurosurgeon and scientist-track investigator in the Developmental Biology Research Program, and an assistant professor of Neurosurgery at U of T.
Brain tumours are the leading cause of cancer mortality in children and remain difficult to cure despite advances in surgery and drug treatments. In adults, most brain tumours are also amongst the most sinister of cancers with formidable resistance to most therapies.
"We found that cancer stem cells from different tumour types, from aggressive malignant tumours to more slow-growing benign ones, share similar properties to each other as well as to normal brain stem cells. This suggests that mutations that lead to cancer formation may have originated in the brain's own small numbers of stem cells," said Dr. Sheila Singh, the paper's lead author, an HSC neurosurgery resident and U of T graduate student who is enrolled in HSC's Clinician-Scientist Training Program.
The biology of the brain tumour stem cell may also shed light on metastases (tumour spread). The non-stem cells in the tumour may break off and spread, but may not be able to grow at distant sites. "It is possible that only the tumour stem cells will be able to grow at distant sites. If this is indeed the case, then the destruction of tumour stem cells may also be important for preventing metastatic disease," added Dr. Dirks.
Next stages of this research involve genetic studies of the purified cancer stem cells to find new genes that are critical for cancer stem cell growth. The identification of these genes is important for determining new targets for brain tumour therapy. Dr. Dirks' laboratory is also investigating whether a patient's cancer stem cells alone can cause growth of the patient's tumour in a mouse. If the tumour resembles the patient's original tumour, this may lead to a mouse model for the tumour type.
Dr. Dirks' laboratory is located in the Arthur and Sonia Labatt Brain Tumour Research Centre at The Hospital for Sick Children. Other members of the research team included Dr. Ian Clarke, Dr. Mizuhiko Terasaki, Victoria Bonn, and Dr. Cynthia Hawkins, all from The Hospital for Sick Children, and Dr. Jeremy Squire from the Ontario Cancer Institute and the University of Toronto.
This research was supported by The Terry Fox Foundation through the National Cancer Institute of Canada, the Neurosurgery Research and Education Foundation with funds from the American Brain Tumor Association, and The Hospital for Sick Children Foundation including gifts from Arthur and Sonia Labatt and the Baker family.
The Hospital for Sick Children, 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. Its mission is to provide the best in family-centred, compassionate care, to lead in scientific and clinical advancement, and to prepare the next generation of leaders in child health. For more information, please visit http://www.sickkids.ca.
Journal
Cancer Research