Discovering new genetic causes of breast cancer

25 July 2012

Montreal, QC -

Innovative research is casting light on new causes of unexplained familial cancers.

 

Dr Francine Durocher of Université Laval is dedicated to discovering new genetic causes of breast cancer, which remain a mystery in three-quarters of familial cancer cases. Her innovative approach has earned her one of 28 new Innovation grants awarded by the Canadian Cancer Society as of July 2012 to research teams across Canada, including 7 in Quebec.

In certain families, breast cancer affects generation after generation of women. Two genes (BRCA-1 and BRCA-2) are known to cause what is called familial cancer. Women who inherit a mutated variant of these two genes face a greater risk of developing breast cancer and must be monitored closely.

These two genes are involved in only one-quarter of familial cancer cases. In the majority of families at risk, the gene or genes involved in causing breast cancer are unknown. Numerous research studies have attempted to identify them, often with disappointing results.

In response to unsatisfactory results, Dr Francine Durocher has sought a different approach. The researcher is focusing on a process, known as alternative splicing, that enables a single gene to produce several different proteins. This is made possible by the fact that the DNA section corresponding to the gene is copied (as messenger RNA or mRNA) in various slightly different versions. In turn, these different copies are used to build different proteins.

Thanks to a previous Canadian Cancer Society grant, Dr Francine Durocher studied 256 families at risk, all of French-Canadian background. Their genetic proximity facilitated her research efforts. Working with these patients, the researcher identified a gene (DNMT3B) of which an alternatively spliced copy is present in many women with breast cancer from high-risk families, but not in their sisters or cousins who are cancer-free. Consequently, this version may be defective.

Dr Durocher has been awarded a $200,000 Innovation grant, which will enable her to understand how this defective copy increases cancer risk, particularly by DNA methylation modification, a process whose role in the development of cancer researchers would like to determine. This new knowledge would allow for more accurate evaluation of the breast-cancer risk that women born in high-risk families face. As a result, some women could be reassured and others followed more closely.

Other projects funded under the Innovation Grants program include:

 

“Pancreas in a dish”: first 3-D model to see how pancreatic cancer develops

Scientists in Toronto have created a tiny, living 3-D organ model of pancreatic ducts to help them conduct research on pancreatic cancer – one of the deadliest and least understood of all cancers. This innovative 3-D organ model could lead to new ways to detect and treat pancreatic cancer, which has a very poor survival rate with only about 6% of patients surviving five years after diagnosis.

The cancer causes few symptoms until it’s in a late, untreatable stage. It is also particularly aggressive, spreading more quickly than many other types of cancer. In 2012, an estimated 4,600 Canadians will be diagnosed with pancreatic cancer and 4,300 will die of the disease. Still, scientists know very little about what causes it and it remains one of the least funded and studied cancers.

With a $200,000 Innovation Grant from the Canadian Cancer Society, Dr Senthil Muthuswamy will use the 3-D biological model he created to unravel the mystery of how pancreatic cancer begins to develop deep within the organ’s duct system. Using thousands of the tiny 3-D models in petri dishes in his lab, Dr Muthuswamy and his team at Toronto’s Princess Margaret Hospital will use genetic manipulation to recreate the events that lead to cancer formation in the pancreas. The researchers will add genes, hormones, and other agents to see what causes the cells to mutate into cancerous lesions. In patients, unfortunately, these lesions progress very quickly to late stage pancreatic cancer.

“In most biological cancer research, we grow and study cells in a flat layer, like a lawn, in a petri dish,” says Dr Muthuswamy. “But cells don’t exist in our bodies like that. They exist as 3-D tubes and vessels, so if you study them in a flat layer, you will not be able to ask all the right questions. These models are much more realistic, much closer to what actually happens in our bodies.”

Dr Muthuswamy and his team will use the 3-D models to observe the different stages of disease. “We’re very excited about this powerful discovery because it’s going to set the stage for identifying new biomarkers and treatments for pancreatic cancer,” says Dr Muthuswamy. “It really takes us to a new dimension.”

Dr Mary Argent-Katwala, Director of Research at the Canadian Cancer Society says, “There is a huge need for more research because pancreatic cancer is one of the most understudied and deadly cancers.” “We are eager to be funding Dr Muthuswamy’s work, which will provide valuable information on understanding how pancreatic cancer develops so it can be diagnosed earlier and treated more effectively. Moreover, this exciting new model will help researchers around the globe in their work on pancreatic cancer.”

Treating cancer with heat and microbubbles

Dr Gregory Czarnota, Sunnybrook Hospital, $200,000 over three years

Heating (hyperthermia) has been used as an add-on to standard radiation therapy, but it has yet to be used as a stand-alone option for treatment. Dr Czarnota is studying the effects of using hyperthermia along with microscopic bubbles and ultrasound – both of which should enhance the heating effects on the tumour – as a treatment option that would be less invasive and more effective for cancer patients.

 

Cancer-killing viruses

Dr Jean-Simon Diallo, Ottawa Hospital Research Institute, $200,000 over 3 years

Dr Robert Korneluk, Children`s Hospital of Eastern Ontario, $200,000 over 3 years

Dr J. Andrea McCart, Toronto Hospital, $200,000 over 3 years

Viruses can be engineered to specifically target cancer cells, leaving healthy cells intact. Drs Diallo, Korneluk and McCart are all taking a unique approach in harnessing the power of viruses to kill cancer cells. Each project involves improving the use of viruses so that they can one day be used in the clinic to treat cancer patients.

 

Preventing hearing loss, a side effect of one type of chemotherapy

Dr François Meyer, CHUQ – Laval University Medical Research Centre, $145,774 over three years

Cisplatin is a drug used for treatment of both childhood and adult cancers, however one of the common side effects of the drug is a loss of hearing. Dr Meyer is the first to conduct a clinical trial with 30 patients using sodium thiosulphate. This natural and safe antioxidant binds to cisplatin molecules. It is injected directly into the ear and, as a result, may block the harmful effect of cisplatin and prevent irreversible hearing loss in adults and children treated with this medication.

Histamines to fight cancer

Dr Jean Marshall, Dalhousie University, $184,448 over three years

While drugs that block histamine and its ability to trigger the immune response are widely used for helping minimize the side effects of cancer treatments, the body’s natural immune response is also thought to be an important player in the fight against cancer. Dr Marshall’s study will take an unconventional approach and look at how histamine can play a positive role in regulating the body’s ability to fight tumours, potentially impacting the way doctors manage many types of cancers.

Detecting lung cancer with a breathalyzer

Drs Haishan Zeng and Stephen Lam, BC Cancer Research Centre, $183,688 over three years

Early detection and treatment of lung cancer increases the 5-year survival rate of the disease to greater than 90%. Drs Zeng and Lam are developing a new biochemical-based breath test for lung cancer screening that will make detection easier and more accessible to health care providers and patients. The test uses a novel, light-based detection system that is fast and inexpensive.

The Innovation Grants

The Canadian Cancer Society today announced 28 new innovation grants. This is the Canadian Cancer Society’s second round of innovation grant funding. The goal of this new program is to support unconventional concepts, approaches or methodologies to address problems in cancer research.

All 28 new projects include elements of creativity, curiosity, investigation, exploration and opportunity. The projects were ranked according to their potential for “high reward” – to significantly impact our understanding of cancer and generate new approaches to combat the disease by introducing novel ideas into use or practice.

As competition for grant funding increases worldwide, peer review panels have become more conservative and risk-averse, emphasizing feasibility more than innovation. It is hoped this grant program will accelerate the introduction of innovation into the entire cancer research system and contribute to the scientific idea pipeline. Grant budgets may be up to $100,000 per year and a maximum of $200,000 per grant. Funding is provided to support the direct costs of research, including supplies, salaries, and equipment associated with the proposed work.

The Canadian Cancer Society is a national community-based organization of volunteers whose mission is the eradication of cancer and the enhancement of the quality of life of people living with cancer. When you want to know more about cancer, visit our website www.cancer.ca or call our toll-free, bilingual Cancer Information Service at 1 888 939-3333.

For more information, please contact:

Melody Enguix

Scientific Communication Advisor

Phone: 514 255-2455