Dr. Jennifer Chan left a position as the pathology leader of Harvard and MIT’s Broad Institute to join the researchers at the University of Calgary. She’s one of several accomplished and promising researchers who now walk the halls of both the Clark H. Smith Brain Tumour Centre and Dr. Samuel Weiss’s brain tumour stem cell core facility. The two labs are in separate buildings – about five minutes apart on foot – at the University of Calgary’s Foothills Medical Centre campus. The 10 or so faculty investigators, like Chan, and the team of graduate students, research assistants, technicians and post-doctoral researchers that make up Calgary’s brain cancer research team, don’t let the five minutes stop them from being good neighbours. The close proximity and relationships are part of what makes Calgary stand out as a centre of excellence in neuro-oncology, or brain cancer, research.
BRAINS: Dr. Jennifer Chan left a position at Harvard to come to Calgary, which is becoming a centre of neuro-oncology excellence.
Photo John Gaucher
The Clark H. Smith Brain Tumour Centre and Dr. Samuel Weiss’s brain tumour stem cell core facility may be located in separate buildings on the University of Calgary’s Foothills Medical Centre campus, but the 10 or so faculty investigators and their team of graduate students, research assistants, technicians and post-doctoral researchers that make up Calgary’s brain cancer research team don’t let the distance stop them from being good neighbours. It takes only five minutes to get from lab to lab, and according to Dr. Gregory Cairncross, head of the department of clinical neurosciences, everyone walks around to see each other all the time. It’s part of what makes Calgary stand out as a centre of excellence in neuro-oncology, or brain cancer, research.
Over the past five or so years, the stars have aligned at the U of C in terms of According to Dr. Gregory Cairncross, head of the department of clinical neurosciences, team members walk between the labs all the time to see each other, and check on the work taking place. He says that over the past five or so years, the stars have aligned at the U of C in terms of facilities, researchers, opportunities and ideas. The environment is collaborative, open and bursting with energy, and it’s given rise to one of the world’s most promising brain cancer research teams. With a long track record of individual successes from the likes of Cairncross, Dr. Stephen Robbins, Dr. Donna Senger and Dr. Jacob Easaw, along with a recent endorsement from the Terry Fox Research Institute in collaboration with the Alberta Cancer Foundation, Alberta Innovates Health Solutions, Genome Canada and others, the Calgary team is working to better understand brain tumours and improve the lives of brain cancer patients.
Chan says that Calgary has long been a respected centre of neuroscience, it’s what brought her to the city in 2008 to join the U of C as an assistant professor in the departments of pathology and laboratory medicine, clinical neurosciences and oncology. According to Cairncross, it was Dr. Peter Forsyth, no longer in Calgary, who pioneered brain tumour research in Calgary and laid the initial foundation for today’s successes, but things really started to click with the establishment of the Clark H. Smith facility in 2004 and the recruitment of people like Chan with complementary and diverse skill sets.
Photo John Gaucher
Cairncross, who came to Calgary in 2002 from Western University, puts it simply: “We work together because we have a common interest, but different experiences and different talents and different perspectives on the problem. This mix fuels discovery.”
Chan came on board after being recruited by Cairncross, who she describes as a “demi-god” in the brain tumour world. Indeed, the man has earned a bit of a celebrity in his field: His self-described “obsession” with a type of tumour prevalent in young adults led him, years ago, to make one of the most significant breakthroughs in brain cancer research to date. Cairncross discovered that oligodendroglioma patients with a certain genetic change responded extremely well to chemotherapy in conjunction with radiation. “Before that, you put a name on brain tumours, but you didn’t know any of the basis for differences,” Chan explains.
Cairncross’s findings changed everything for patients with these particular tumours. With the new therapy, their average lifespans doubled from five-to-10 years to 10-to-20, with no decrease in the quality of life. His clinical study, which took 20 years to complete, is about to be published, but Cairncross’s combined method of treatment has already become standard practice in oligodendroglioma management. Doctors treating it gambled that he was right before the study was completed, and their bets paid off. “The work I have done on oligodendrogliomas over the past 20 years had led to the treatment we use today, the approach we use today, the diagnostic assessment of the cancer we use today. It has really defined the standard of care of that illness today,” Cairncross says.
Twenty years may seem like an eternity, but Chan looks to the recent past to put things into perspective. “In the 1940s and earlier, treatments were limited. You could try to cut out a cancer – perform surgery – but there was little in the way of medical therapy. Although some radiation was used, there was no chemotherapy. The modern practice of multiple approaches and combined therapies to target cancers just didn’t exist,” she says. “In 60 years there are now cancers that are very well treated. Those people had death sentences before.”
Clearly, incremental changes accumulate, and it’s these that add up to transformative changes. The details are what Chan focuses on in her work at the Clark H. Smith, bridging the gap between basic science and clinical research. One of her major roles is creating better animal models of cancer – whether by injecting mice with human cancers, or introducing mutations into genes that are abnormal in human cancers – a vital step in taking a therapy from the petri dish to the patient.
Chan’s other major role is directing the Clark H. Smith Neurologic and Pediatric Tumour Bank, a tissue bank stocked with high-quality tumour samples and corresponding blood and urine samples from upwards of 700 patients. Initially established by Dr. Peter Forsyth, the tumor bank has grown to become a critical component to many research projects within the Clark Smith Brain Tumour Group and beyond. Unlike many tissue banks, which simply “get a glob of tissue, stuff it in a tube and throw it in the freezer,” the Calgary bank, together with the closely associated Stem Cell core, is now highly curated, quality-controlled at every stage, and contains live cultured or cryogenically preserved tissue samples from many of its malignant brain tumour donors. Chan advises other investigators on how human tissue might be best used to address their scientific questions in order to bring the relevance of their findings to human disease. Where many other tissue banks can be equated to Walmarts, Chan describes her smaller but high-quality and interactive bank as “boutique” in the brain tumour world.
PIONEER: Dr. Gregory Cairncross says, “When there’s a cluster of people that share the same interest good things happen.”
Photo John Gaucher
A major recent success for Chan’s tissue bank has been the establishment of two cell lines from an extremely rare, ultra-aggressive pediatric brain tumor known as ETANTR. One of these lines came from a two-year-old Calgary boy, Alexander Brown, whose parents donated his tumour when he died in late 2010. In Chan’s lab, mice injected with Alexander’s live cells are currently being used in research in order to better understand the biology of ETANTR. His tissue has been sent to labs worldwide for study and genetic sequencing, and work on it continues.
For Brown’s parents, Tara and Jonathan, who run a wish-granting foundation called Alexander’s Quest, the chance to contribute to ongoing research gives Alexander’s life true meaning. “A part of Alexander is still growing and the cancer hasn’t won yet. Cancer took Alexander, but now the cancer works for us and works for all the other children that have ETANTR,” Jonathan says. He champions tumour banking and the work being done at the University of Calgary. “You never know, working on ETANTR, they might discover something that works on other tumours as well. The battle continues and a part of Alexander is still alive and still fighting.”
But growing brain tumour tissue is no easy matter, and that’s where the collaborative nature of Calgary’s brain tumour research team really shines. Neuroscientist Weiss is the director of the Hotchkiss Brain Institute and a stem cell researcher whose interest in brain tumours began fairly recently, explains Cairncross. But it’s clear why Weiss’s curiosity might have been piqued. “It turns out that these stem cells might actually be the cells that give rise to brain cancers, and you can grow brain cancers of all types, especially glioblastomas, if you grow them the way Sam grew normal cells from the brain,” Cairncross says. Weiss’s method of growing tumours preserves the genetic structure of the cells in a much better way than previous methods have. “Now we have a much better replica of the human disease in the laboratory to study on a daily basis.”
It’s those glioblastomas – the most common brain cancer in adults and, to date, one of the most resistant to any advances in treatments – that make up the focus of the Calgary team’s latest project. The new effort – a drug discovery development program for brain cancers funded by $8-million in grants from the Terry Fox Research Institute, the Alberta Cancer Foundation and others – reaches nation-wide. Researchers from the Calgary team will grow glioblastomas in the stem cell culture method developed by Weiss; a team at the Genome Sciences Centre at the University of British Columbia will sequence the genetic structure of the cancers; and drug screening will take place in Toronto against the multi-thousand compound libraries located there. Team members will test promising compounds in mice with human cancers in Calgary before clinical trials commence through the National Cancer Institute Canada Clinical Trials Group, based at Queen’s University in Kingston, Ontario.
Although the Terry Fox project is in its early days, it’s already yielding results. “We have some interesting drugs that work in the cells in the laboratory, and we’re just trying to figure out how well they work, and if they’ll work when they’re grown in mice, not Petri dishes. We’re working on all these steps, and hope that one of these compounds will be in human testing in the next few years,” says Cairncross.
As to why Calgary’s become such a centre for innovation and excellence in brain tumour research, Cairncross isn’t quite sure. Perhaps there’s a bit of serendipity involved. “It happens periodically in fields that, for some reason, there’s a cluster of people who are in the same place at the same time for their own reasons that share the same interests, and good things happen.”
For her part, Chan feels there are many more good things to come from the Calgary brain tumour research team and the collaboration happening between scientists, clinicians and patients. “The attitude here is that we’re going to work together, and I like that. Look at the success of some of our recent work – based on that, we’ve got an endorsement from larger funding agencies to expand our efforts. I think that’s very positive.”