Stand Up To Cancer Canada Announces New Cancer Stem Cell Dream Team To Attack Brain Cancer in Children and Adults

A team of top Canadian scientists, including leading pioneers of stem cell research, was named today to lead a new attack on brain cancers in children and adults, using genomic and molecular profiling technologies to focus on the cancer stem cells that drive the growth of tumours.

“Brain tumours are not as common as many other forms of cancer, but they are devastating, especially when they strike the very young,” said Phillip A. Sharp, PhD, Nobel laureate and institute professor at the Massachusetts Institute of Technology’s David H. Koch Institute for Integrative Cancer Research and co-chair of the Stand Up To Cancer (SU2C) Canada Scientific Advisory Committee (SAC). “The Dream Team will bring new insights to brain cancer research, which has been an underfunded area.”

The leader of the SU2C Canada Cancer Stem Cell Dream Team: Targeting Brain Tumour Stem Cell Epigenetic and Molecular Networks, is Peter B. Dirks, MD, PhD, neurosurgeon and senior scientist at The Hospital for Sick Children (SickKids) in Toronto, who was the first to identify cancer stem cells in brain tumours in 2003. The co-leader is Samuel Weiss, PhD, director of the Hotchkiss Brain Institute and professor in the Cumming School of Medicine at the University of Calgary, who was awarded the Canada Gairdner International Award in 2008 in part for his discovery of adult neural stem cells in the brains of adult mammals.

“Stem cells and cancer stem cells were discovered in Canada,” said Alan Bernstein, OC, PhD, president and chief executive officer of the Canadian Institute for Advanced Research (CIFAR) and co-chair of the SU2C Canada SAC. “By bringing together a top-flight team of scientists and clinicians from across Canada and applying what we have learned about brain cancer and cancer stem cells, our hope is that novel treatments will be developed.  Treatments that will extend the lives of patients, and give new hope to children and their parents, as well as adults who struggle with these devastating diseases.”

Funding of CA$11.7 million  over four years is being provided by SU2C Canada, Genome Canada, the Canadian Institutes of  Health Research (CIHR), the Cancer Stem Cell Consortium (CSCC), and the Ontario Institute for Cancer Research (OICR), which will provide up to CA$1.2 million for clinical trials in the province of Ontario.  The American Association for Cancer Research International – Canada is SU2C Canada’s scientific partner.

“Brain tumours in children and adults contain a small number of cells called stem cells that resist treatment and continually regenerate, driving tumour growth and recurrence after initial responses to treatment,” Dirks said. “Our team will conduct multiple analyses of brain cancer stem cells, profiling their biological makeup to identify drugs that are likely to block the uncontrolled growth of the tumours, and carry out clinical trials across Canada to find the safest and most effective drugs to treat these cancers.”

Federal ministers welcomed the new Dream Team.

“My heartfelt congratulations to the Dream Team researchers who are collaborating to pave the way to better and faster cancer treatments for Canadians and people around the world,” said the Honourable Kirsty Duncan, Minister of Science. “In supporting the Dream Team, the Government of Canada is investing in promising discoveries that could improve the outcome of patients who live with brain cancer.”

“Canada is a leader in stem cell research, and the Dream Team is carrying on this proud tradition,” said the Honourable Jane Philpott, Minister of Health. “I am optimistic that this team of top Canadian scientists has what it takes to find new ways of fighting brain tumours and improve the lives of children and adults living with brain cancer.”

“Ontario is proud to support leading researchers, including top stem cell scientists, through the Ontario Institute for Cancer Research. Finding new and innovative ways to treat brain cancer in children and adults brings hope to patients and their families,” said the Honourable Reza Moridi, Ontario Minister of Research and Innovation.

The team will focus on glioblastomas in adults and children and on posterior fossa ependymomas of infants, both of which have a dismal outlook for patients and for which treatment options are limited. Less than 10 percent of adults are living five years after a glioblastoma diagnosis. In children, cancers of the brain and central nervous system are the No. 1 pediatric cancer killer, even though leukemia is the more common pediatric cancer.

“It’s like a Peter Pan syndrome, in which the immature cell, the stem cell, never grows up,” said Michael D. Taylor, MD, PhD, a neurosurgeon and senior scientist at SickKids who specializes in cancer genomics, epigenetics, and chromatin biology, and serves as a principal investigator on the team. “Our objective is to take those cancer stem cells and convince them to quit multiplying and leave the rest of the brain alone.”

“This Dream Team approach not only brings together the best researchers from across Canada, but integrates pediatric and adult brain cancer research. Pediatric cancer research is often essential to inform adult cancer research,” added Taylor, who also serves as a principal investigator on the U.S.-based SU2C-St. Baldrick’s Foundation Dream Team on childhood cancers. 

Researchers have found that these cancers contain brain tumour stem cells (BTSCs). While similar to nerve stem cells that mature during normal brain development, abnormal programming in BTSCs allows them to drive tumour relapse (or the ability of the tumours to grow back again) and drug resistance. The Dream Team’s goal is to understand the abnormalities in BTSCs so that they can identify vulnerabilities that can be used to develop new drugs that are effective against brain cancers.

To achieve this goal, the Dream Team will take a three-pronged approach to understanding and targeting brain cancer stem cells that resist treatment and fuel tumour regrowth. Their first approach is to perform detailed analysis of BTSCs taken from 70 different glioblastomas or ependymomas and grown in the laboratory. They will use cutting-edge technology to understand the full biological profile of these cells – from changes in the cells’ genetic codes to epigenetic programs that control when genes are turned on or off and alterations in the way the cells metabolize nutrients.

The Dream Team’s second approach will be to screen a collection of chemicals on the same BTSCs for potential new drugs and drug combinations that are effective against these cells. Finally, while they are learning about the biology of BTSCs and screening for new compounds, the Dream Team will test five new potential drugs that they have already identified as very promising by tests performed in laboratory mice to find out which drugs or drug combinations might kill glioblastomas or ependymomas. The Dream Team hopes to bring new drugs for brain cancer into clinical trials in the third and fourth years of their research funding.

“Our understanding of brain cancer stem cells and their role in causing tumours to grow is advancing very rapidly, with significant contributions coming from Canadian scientists that are part of this exciting new Dream Team,” Weiss said. “Our proactive, data-sharing approach, coupled with strategic partnerships with multiple, major pharmaceutical companies, will help accelerate the search for effective treatments.”

In addition to Dirks, Weiss, and Taylor, the team’s principal investigators are:

• Cheryl H. Arrowsmith, PhD, senior scientist at the University Health Network (UHN) in Toronto (structural and chemical biology);
• Gary D. Bader, PhD, associate professor at the University of Toronto (computational biology and cancer bioinformatics);
• Amy A. Caudy, PhD, assistant professor in the Department of Medical Genetics and Microbiology at the University of Toronto (metabolomics and 2-hydroxyglutarate biology);
• Nada Jabado, MD, PhD, senior scientist/professor, Research Institute of the McGill University Health Centre/McGill University (pediatric brain tumour genomics and epigenomics);
• Mathieu Lupien, PhD, scientist at UHN (cancer genomics, epigenetics, and chromatin biology);
• Marco A. Marra, PhD, director of the British Columbia Cancer Agency Branch in Vancouver (human and cancer genomics); 
• Trevor Pugh, PhD, scientist at UHN (clinical and cancer genomics);
• Michael Salter, MD, PhD, director of The Hospital for Sick Children Research Institute (neurobiology and synaptic plasticity); and
• Michael D. Tyers, PhD, professor at the University of Montreal (proteomics and systems biology).

Serving as advocate on the team is Wendy M. Durigon, of Guelph, Ontario, founder of Jessica’s Footprint Foundation, named in honour of her daughter Jessica, who died of brain cancer in 2003 when she was just a year old.

“Genome Canada is proud to participate in this new Dream Team that is tackling a very tough problem in cancer genomics,” said Marc LePage, president and chief executive officer of Genome Canada. “Canadian scientists lead the world in this complex field, and we are certain their expertise will lead to progress against brain cancer.”

“Targeting cancer stem cells is a key piece of the puzzle to improving outcomes for brain tumour patients,” said Dr. Stephen Robbins, scientific director of the Canadian Institutes of Health Research Institute for Cancer Research. “The Dream Team’s research will help us understand how the cancer progresses and how to stop it.”

“The Ontario Institute for Cancer Research is proud to support the clinical trial component of this exciting project, ensuring there is a clear path to the clinic for the team’s research discoveries and that patients will benefit from this work as soon as possible,” said Thomas J. Hudson, MD, president and scientific director of OICR. “These clinical trials will be conducted here in Ontario, which has a long and successful history in cancer research and in cancer clinical trials.”

The SU2C Canada Cancer Stem Cell Dream Team is the second Dream Team to be announced by SU2C Canada. The first was the SU2C Canada – Canadian Breast Cancer Foundation Breast Cancer Dream Team. SU2C Canada is a project of EIF Canada, a Canadian registered charity.

As the scientific partner to SU2C Canada, the AACR International – Canada, the Canadian arm of the world’s largest scientific organization devoted to cancer research, is responsible for administering the research agreement and providing oversight to ensure that progress is being made.