ARCHIVED - Your Health Research Dollars at Work 2005-2006

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Cancer

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The Canadian Institutes of Health Research (CIHR) is the Government of Canada's agency for health research. Through CIHR, the Government of Canada invested approximately $118.3 million in 2005-06 in cancer research across Canada.

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The Facts

• Canada is facing a cancer epidemic over the next 20 years, due to our aging population. If current trends continue, 5.7 million Canadians will develop cancer and 2.7 million will die of the disease over the next 30 years.
• An estimated 153,100 new cases of cancer and 70,400 deaths from cancer will occur in Canada in 2006.
• Lung cancer is the leading cause of cancer death for both men and women. Overall, colorectal cancer is the second leading cause of death from cancer.
• Canadians aged 70 and over represent 43% of new cancer cases and 60% of deaths due to cancer.
• 38% of Canadian women and 44% of men will develop cancer during their lifetimes based on current incidence rates.
• 24% of women and 29% of men, or about a quarter of all Canadians, will die from cancer, based on current mortality rates.
• Smoking is responsible for 27% of potential years of life lost due to cancer.
• Cancer costs Canadians more than $14 billion every year. Of that total, $2.5 billion is for direct costs such as hospitalization and medication, while $11.8 billion is for indirect costs such as early death or disability.

Research Finding Solutions to Cancer

• CIHR-supported researcher Dr. Georg Bjarnason, from Sunnybrook Health Sciences Centre in Toronto, has determined that head and neck cancer patients who receive high doses of radiation in the morning have a greater chance of avoiding mucositis (a severe irritation of the throat and mouth). In his study, Dr. Bjarnason discovered that only 43% of patients who received radiation therapy in the morning developed mucositis, compared to 67% in the afternoon. The discovery could have implications for other cancer therapies with equally serious side effects.

• So-called "natural killer" (NK) cells recognize and kill cancer cells. Health research teams have been trying for many years to find out how to increase NK cell activity. Now, CIHR-supported researcher Dr. André Veillette, from the Institut de recherches cliniques de Montréal, has discovered that a protein called EAT-2 slows down the function of natural killer (NK) cells. If medications that suppress EAT-2 in humans can be developed, Dr. Veillette believes that NK cells will likely increase and work in conjunction with chemotherapy and radiotherapy to improve the effectiveness of cancer treatments.

• The spleen, which filters and produces blood, is not considered essential for normal body function. But CIHR-supported research Dr. Yaacov Ben-David, from Sunnybrook Health Sciences Centre in Toronto, has determined that the spleen in diseased mice can play a role in the development of leukemia. Some of the growth factors released by the spleen, such as MCP and VEGF, may promote the development of leukemia-based cells, as well as breast and other types of cancers. Should Dr. Ben-David's discovery prove to be equally true in humans, the development of new drug therapies or even the removal of the spleen through surgery could become treatment possibilities.

• It's been known for some time that the overproduction of a protein known as c-Myc plays a key role in the development of cancer. Work by CIHR-supported researcher Dr. Sabine Mai of the University of Manitoba has uncovered a new function for this protein, demonstrating that when c-Myc is present at a certain level, the ends of chromosomes become "sticky" and join together. When the cell divides, these conjoined chromosomes break apart, but at a different location. This cycle continues as these now altered chromosomes attract new chromosomes and break in new locations, creating genetic instability and leading to uncontrolled growth of cells. New insights into how cancer develops are key to finding new ways to diagnose and treat cancers.

• Dr. Peter Forsyth, from the University of Calgary, and Dr. Grant McFadden, from the Robarts Research Institute in London, Ontario, have shown for the first time that a live poxvirus, called the myxoma virus, can kill human brain tumours in mice. In their cross-country, collaborative study, Drs. Forsyth and McFadden, both recipients of CIHR funding, showed that the poxvirus eradicated human gliomas, or terminal brain tumours, in 92% of the mice tested. Only cancer cells died, while all other healthy cells remained intact. Should further animal testing prove to be successful, human clinical trials could start in about three or four years.

• Dr. Martin Yaffe, from Toronto's Sunnybrook Health Sciences Centre, has obtained evidence from a clinical trial that digital mammography is more accurate than film mammography in detecting breast cancer earlier in women who are under 50, have dense breasts, or are premenopausal. CIHR funding supported the development of the new digital mammography technique.

In the Pipeline...
Addressing the Challenge of Breast Cancer

A research team lead by Dr. Michael Pollak from McGill University and including researchers from Université Laval, UBC and Mount Sinai Hospital is investigating the possibility that Vitamin D deficiency and high levels of insulin could increase breast cancer risks. Joint funding from CIHR and the Canadian Breast Cancer Research Alliance is helping to support the research.

The Researchers...
Dr. Peter Cheung - Mapping What Lies Beyond the Human Genome

Major accomplishments are never the end of the story. More often, they're an invitation to begin a new chapter. That's certainly the case in the field of genetics and it clearly applies to Dr. Peter Cheung, who is exploring the complex factors controlling gene regulation, research with future uses in cancer treatments.

"The human genome sequencing and gene mapping projects gave us a lot of information. Now we need to go to the next step and figure out how all of these genes are regulated and how changes in the environment can cause genes to switch on or off," notes Dr. Cheung. This new field is known as epigenetics.

For Dr. Cheung, a CIHR New Investigator and Assistant Professor at the University of Toronto, understanding gene regulation is essential in understanding cancer, which, in plain terms, represents a failure in this regulation.

"There are more than 200 different cell types in the body, each with a highly specialized function. Each of these cells has the same copy of genome sequences. But for them to carry out their own special functions, each cell type has unique sets of genes that are expressed. Regulation is like directing traffic - telling the cell which genes are needed, and thus activated, and which ones are not required and therefore can be silenced," he says.

Key to this puzzle, Dr. Cheung is studying chemical modifications made to a group of proteins known as histones. DNA is always spooled around histones, like silk thread around a bobbin, to make chromosomes. Histones, therefore, control the accessibility of the DNA and genes. Histones have "tails" which can attract various chemicals, an acetyl group here, a methyl group there, and so on.

These chemicals, in turn, change the tension of the DNA spool. An acetyl, for example, is like a muscle relaxant, causing the DNA to loosen. In this state, it gives access to so-called transcription factors that, ultimately, will lead to gene activation. Methyl groups create the opposite effect.

With cancer, these seemingly distant and minor chemical modifications can end up having a major impact, e.g. a tumour suppressor might accidentally get turned off and result in the development of cancer. Dr. Cheung's research points to new opportunities for cancer therapies, efforts that focus less on the DNA sequences of genes and more on the machinery controlling them.

"We are just beginning to understand the different players involved in histone modifications, and we're now trying to focus on how they work together to regulate gene expression. We need to find the right chemicals to help tweak these players, to find activators and inhibitors which will create better control and better outcomes," Dr. Cheung concludes.

The CIHR Institute

CIHR's Institute for Cancer Research has been coordinating cancer research across Canada in priority areas such as palliative and end-of-life care, establishing a model for the world. Other priorities run the range from molecular profiling of tumours to early detection of cancer, to preventing the risk behaviours that can lead to cancer.

About CIHR

The Canadian Institutes of Health Research (CIHR) is the Government of Canada's agency for health research. CIHR's mission is to create new scientific knowledge and to catalyze its translation into improved health, more effective health services and products, and a strengthened Canadian healthcare system. Composed of 13 Institutes, CIHR provides leadership and support to more than 10,000 health researchers and trainees across Canada.

Canadian Institutes of Health Research
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http://www.cihr-irsc.gc.ca/