Most days, Dr. Paola Marignani spends her time zapping healthy cells with anywhere from 15 years to 20 years of instant DNA damage. Why? To study their transition from a healthy cell into a cancerous state. But for one day in September, the Dalhousie Medical School professor and cancer researcher traded in her lab coat for an apple-picking apron.

 

Marignani was headed to Nova Scotia’s Annapolis Valley to spend the day picking apples for cancer research. She and her research team were partnering with Bosom Buddies, a grassroots group of women cancer survivors that has raised more than $200,000 for breast cancer research and support programs in Nova Scotia, largely through making and selling apple pies throughout the province. “I draw from their energy and passion,” says Marignani, who made pastry with Bosom Buddies members last year and regularly talks to cancer groups about her research. “As scientists, we can’t be distant; we have to reach out.” She hopes that public awareness and support will lead to more federal investment in cancer research.

 

The need for investment is vital, not just in terms of cancer’s human toll but also because of its looming impact on Canada’s economy. “The prevalence of cancer is projected to increase 50% to 55% over the next 20 years, but within the labour force it’s projected to increase 100%,” says Paul Smetanin, the president and CEO of RiskAnalytica, a Toronto–based risk-management science firm. “Think of it this way: cancer rates are up, and so is the economy’s dependence on an older workforce, a population commonly associated with cancer. Plus, more women are in the workforce, and more and more women are being affected by breast cancer at a younger age. Add these compounding factors up, and you get a 100% increase.”

 

Through his work in developing the Canadian Strategy for Cancer Control, Smetanin has built the business case for almost all aspects of cancer control. “Cancer has a

one-two impact,” he says. “It takes from the pockets of a community, like costs of hospitals, while also impacting what you can put back into the community, like the ability to produce an income. Research and improved treatments are expensive, but if you can extend lifespans, it’s a benefit to society.” The key, he insists, is to put the resources where they will make the most impact: prevention strategies, clinical guidelines, and reintegrating cancer patients back into communities (see “Cancer packs an economic punch,” page 43).

 

Marignani’s research focus is tumour suppressors. When present, these proteins prevent cancers from forming. However, she has discovered a key tumour suppressor for breast cancer called LKB1 that, when genetically mutated, can actually cause cancer. Prior to this, it was believed only the loss of a suppressor could cause cancer. Her findings were recently published as a priority report in the American Association for Cancer Research’s Cancer Research journal. Marignani’s goal is to find a way to repair DNA damage so mutated tumour suppressors can regain their role as cancer fighters.

           

Marignani joined Dalhousie Medical School in 2003 from the Toronto–based Ontario Cancer Institute. She was among the first of a wave of cancer researchers who has surged into the region since the launch of the Dalhousie Cancer Research Program (DCRP) in 2001. More than a dozen others have joined Dalhousie’s Faculty of Medicine in the past few years, swelling the ranks of cancer researchers and driving a more than threefold increase in annual cancer funding at the medical school.

 

It all started with a single remarkable act. In 1999 Beatrice Hunter, a Nova Scotian, bequeathed $13 million to the Dalhousie Medical Research Foundation (DMRF) for cancer research, in memory of her parents, Dr. Owen and Mrs. Pearle Cameron. Now called the Cameron Endowment, it has grown to $17 million and generates more than $500,000 each year for cancer research at Dalhousie. The sudden arrival of this stable local funding inspired DMRF and Dalhousie Medical School to join forces with Cancer Care Nova Scotia (CCNS) to form the DCRP. The new program fosters a world-class cancer research effort through community building, training, and recruitment initiatives.

 

The growth of cancer research since is a prime example of what vision and money can accomplish together. “The endowment, combined with the vision of the partners to create the DCRP and make some key recruits, has had an exponential effect,” says Dr. Eva Grunfeld, the chair of the DCRP.

 

The recruitment of cancer research pioneer Dr. Patrick Lee in 2003 turned scientific heads around the globe. Lee is renowned for his discovery that a common and benign virus called human reovirus targets and kills cancer cells without harming healthy cells. He’s currently pushing new frontiers, exploring the potential of reovirus to eradicate cancer stem cells, the insidious mother cells that must be destroyed to halt cancer at its source. At the same time, he is studying a crucial tumour-suppressor protein called p53, which prevents DNA-damaged cells from becoming cancerous. “Learning how p53 works and why it loses its protective function in cancer could well lead to a cure,” says Lee.

 

As Dalhousie Medical School’s first Cameron Chair in Basic Cancer Research, Lee is attracting international attention to the university’s cancer research effort and attracting top-notch researchers. These include Dr. David Waisman, who is testing ways to

cut off tumour blood supply and prevent metastasis, or spreading, and Dr. Christopher Richardson, who is working with the Mayo Clinic on measles-based cancer therapies while studying how hepatitis B and C cause liver cancer.

 

It’s all part of building human capital in the life-sciences sector. The growing cadre of high-profile senior researchers has, in turn, attracted junior researchers, postdoctoral fellows, graduate students, and, of course, all-important funding. “Every dedicated researcher who brings a set of skills attracts funds, and that generates a huge domino effect,” says Grunfeld, herself one of those key senior recruits. A world authority in cancer survivorship and follow-up care, she came to Halifax in 2004 from the University of Ottawa. In addition to leading the CCNS Cancer Outcomes Research Program and chairing the DCRP, she is a professor and an active staff member in the Division of Medical Oncology at Dalhousie University and Capital Health, Nova Scotia’s largest health district.

 

Grunfeld recently reeled in a five-year, $1.5-million grant through the Canadian Institutes of Health Research’s (CIHR) New Emerging Team Grants competition, to study the accessibility and quality of colorectal cancer care in Nova Scotia. Dalhousie Medical School, Capital Health, the Nova Scotia Department of Health, CCNS, and DMRF provided local matching funds, but it was the quality of the science that most impressed the jury.

 

“This is the first study in Canada that will examine colorectal cancer across the entire cancer-control continuum,” says Grunfeld, “from screening through to palliative

care, in an entire population.” She describes the process of writing a grant involving 19 co-investigators as “Herculean,” but the resulting proposal ranked second in the country in this fiercely contested competition.

 

With the new grant, Grunfeld now holds nearly $2.5 million in peer-reviewed funding. Most of this money goes to salaries and creates opportunities for young people in fields as diverse as data management, statistics, health systems management, qualitative research, and even journalism.

 

For her, the laboratory isn’t an equipment-filled room but instead represents the health system and the people it screens, diagnoses, and treats. “My research evaluates health services,” she says, “and identifies specific ways to improve quality and cost effectiveness.”

 

The involvement of CCNS and the Nova Scotia Department of Health means the findings of the colorectal cancer study will be applied quickly to improve care and shared with other provinces facing similar challenges. “We know we need to improve screening,” says Grunfeld, “and to streamline the journey from symptoms to treatment.”

 

This and other work underway throughout the Atlantic region hearkens to Paul Smetanin’s remarks about spending resources where they will make the most impact. “Cancer’s cost to the health care system and society is enormous and growing,” says Warren McKenzie, who co-founded the New Brunswick Innovation Foundation in Fredericton and also chairs the Fredericton–based Populomix Cancer Research Institute. “Targeted spending on research to catch cancer early is the most effective way to reduce the burden.” McKenzie recently finished a term on the board of the world-leading Fred Hutchinson Cancer Center in Seattle and has joined the board of NRC-IIT, the National Research Council Institute for Information Technology.

 

At the Fred Hutchinson Cancer Center, affectionately known in the research community as The Hutch, McKenzie worked closely with its president and director, Dr. Lee Hartwell, an advocate for early detection and the winner of the 2001 Nobel Prize in Medicine. “Lee Hartwell has this slide he uses in presentations,” relates McKenzie. “It’s a grid showing that survival rates for undetectable forms of cancer have not improved much since the 1950s. Most of our gains have been due to earlier detection.”

 

McKenzie is pressing the early detection agenda in Atlantic Canada, linking key institutions through Populomix. Board members so far represent Dalhousie Medical School, University of New Brunswick, Université de Moncton, the Atlantic Cancer Research Institute, NRC-IIT, and the New Brunswick Innovation Foundation. McKenzie believes that Populomix is a means of pooling the region’s resources and working co-operatively, with a focus on discovering and testing the diagnostic potential of biomarkers.

 

 

Biomarkers are molecular changes that indicate that a cancer is beginning. Fundamental research into the origins and early stages of cancer is as critical to identifying biomarkers as it is to developing strategically targeted therapies. That’s why Dalhousie’s Dr. Mark Nachtigal studies the biology of ovarian cancer. Having lost several close family members to ovarian cancer, he feels keenly the need for diagnostic markers and improved treatments. “There are few obvious symptoms in the early stages,” he says, “so it tends to go undetected until it erupts.”

 

Biomarkers may take the form of a unique pattern of gene or protein expression; in other words, genes may be turned on or off in unusual ways. But with more than 30,000 genes in every human cell, it is no mean feat to identify patterns that signal cancer. Nonetheless, researchers at NRC-IIT in Moncton and at the Atlantic Cancer Research Institute (ACRI), in Moncton, have identified signature patterns for prostate cancer and colon cancer. They have achieved this by combining ACRI’s rapid DNA microarray analysis technology with NRC-IIT’s mathematical and bioinformatics expertise.

 

The prostate biomarker is more than 96% accurate in detecting prostate cancer, compared to the traditional PSA blood test, which only identifies about 70% of cancers. “The potential of biomarkers to revolutionize cancer care is staggering,” says Dr. Rodney Ouellette, the CEO and director of discovery at ACRI and a vice-chair of Populomix. “In most cases, if you can catch cancer early enough, you can remove it surgically for a complete cure.”

 

Biomarkers may even have the potential to diagnose a predisposition to a certain form of cancer. “This would call for heightened surveillance and the possibility of very early intervention,” notes Warren McKenzie. “Perhaps a tumour suppressor like p53 could be restored to block the cancer.”

 

Technology is vital in this endeavour, not only for laboratory analysis but also for population data analysis. “As new biomarkers are discovered, we need a systematic way to validate them,” says Dr. Gerry Johnston, the associate dean of research at Dalhousie Medical School and the co-chair of Populomix. “The only way to verify reliability is through long-term population cohort studies.”

 

A leading cancer researcher who studied with Lee Hartwell before joining Dalhousie 30 years ago, Johnston has long been a driving force behind the advancement of cancer research in Atlantic Canada. He sees the potential for the region to carve a unique niche in the global cancer research arena. “The Hutch is keen on seeing the Atlantic region develop as a population resource,” says Johnston. “They are already involved in biomarker initiatives in the Pacific Rim, but because of our lifestyle and high rates of cancer, findings in this population are relevant to the North American context.”

 

As it turns out, population studies of the kind done in Canada are not even possible in the

United States—a fringe benefit of our public health care system. Atlantic Canada has the added advantages of a stable population, health records that go back generations, relatively few entry points to the health care system, and a wealth of linkable databases.

Dr. Louise Parker describes the region as “epidemiology heaven.” Previously a senior epidemiologist in England, Parker came to Canada in 2006 to join Dalhousie and the IWK Health Centre. This fall she was appointed the first Canadian Cancer Society (Nova Scotia Division) Chair in Population Cancer Research. She will play a vital leadership role in future regional cohort studies, through Populomix and other consortiums. She already has studies in progress to investigate the links between obesity and cancer.

 

“Population studies allow us to see what’s happening now and to find ways to alter the trajectory of cancer,” says Parker. “We can investigate genetics, environmental exposures, lifestyle, screening behaviour, and so on, to see what differs between people who develop cancer and those who don’t.”

 

As a testing ground for biomarkers, Atlantic Canada stands to benefit by early access to new diagnostics. On top of this, it’s an opportunity for the public to get directly involved in research. “Public understanding and support is crucial, but it’s also research that will engage the public as key players,” says Johnston, adding that response rates to calls for research involvement tend to be high in the region. Adds Parker, “There seems to be a strong sense of pride in being part of Atlantic Canada, a real willingness to help out.”

 

This is a good thing, because Atlantic Canada suffers from cancer rates 10% to 20% higher than the rest of the country. As overall cancer rates rise, this dreaded family of diseases will take an even greater toll here. “The problem of cancer is too big to be tackled in isolation,” says Johnston. “We need to pool our resources regionally, engage the public imagination, and form national and international collaborations.”

 

Meanwhile, Dr. Paola Marignani and her lab team continue to study and raise money for cancer research. Most recently, they participated in the annual CIBC Run for the Cure. Donning brightly painted lab coats and calling themselves The Tumour Suppressors, they walked as a group of interacting proteins. Marignani’s team has raised more than $10,000 for the Canadian Breast Cancer Foundation in the past three years. “This is a great way to talk about our research,” she says.