"Now that we have confirmed that a small number of cancer stem cells initiates and maintains human brain tumour growth in a mouse model, we can potentially use the mouse model with each patient's tumour cells to see if therapies are working to conquer that patient's tumour," said Dr. Peter Dirks, the study's principal investigator, a scientist and neurosurgeon at Sick Kids, and an assistant professor of Neurosurgery at U of T. "A functional analysis of the brain tumour stem cell may also give new insight into patient prognosis that may then warrant individual tailoring of therapy."
Dr. Dirks' laboratory was able to regrow an exact replica of patients' brain tumours in a mouse from the isolated cancer stem cells, or brain tumour initiating cells. They were then able to study the growth of the human brain tumour in the mouse model using the advanced imaging technology in the Mouse Imaging Centre (MiCE) at Sick Kids.
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 among the harshest cancers with formidable resistance to most therapies.
"Next, we are going to study the gene expression of the brain tumour stem cells. Once we have identified what genes are expressed in those cells, we will then be able to target these genes using new drugs or genetic-type therapies," said Dr. Sheila Singh, the paper's lead author and Sick Kids neurosurgery resident and U of T graduate student who is enrolled in Sick Kids' Clinician-Scientist Training Program. Dr. Singh was supported by a fellowship from The Terry Fox Foundation, as well as by funding from the Neurosurgical Research and Education Foundation and the American Brain Tumor Association.
"We have shown that it is really worthwhile to invest further in studying brain tumour stem cells, as we will be able to determine if current therapies are failing because they are not stopping the cancer stem cells," added Dr. Dirks. "It also looks like cancer stem cells play a role in other solid tumours such as breast cancer, so we can all work together to develop new treatments for these cancers."
Other members of the research team included Dr. Cynthia Hawkins, Dr. Ian Clarke, Dr. Takuichiro Hide and Dr. Mark Henkelman, all from Sick Kids, Dr. Jeremy Squire and Jane Bayani from the Ontario Cancer Institute, and Dr. Michael Cusimano from St. Michael's Hospital.
This research was supported by the Canadian Cancer Society, the Canadian Institutes of Health Research and Sick Kids Foundation (including support from BrainChild, the Jack Baker family fund and the Jessica Durigon family fund). MiCE is supported with funding from the Canada Foundation for Innovation, Ontario Innovation Trust, the Ontario Research and Development Challenge Fund and Sick Kids Foundation.
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.