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Breast Cancer Awareness Month: Profile of a Dedicated Researcher

Oct. 29 2020 | Cancer

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Breast cancer is the most common form of cancer in women in Canada, after certain skin cancers. It accounts for ¼ of cancer diagnoses and 13% of all cancer deaths, making it the 2nd leading cause of death among Canadian women. This Breast Cancer Awareness Month reminds us that breast cancer is a very real threat to Canadian women.
 
However, cancer is not invincible. Today, the 5-year breast cancer survival rate is 88%, one of the highest. This is the result of relentless scientific research, carried out by dedicated researchers such as Jean-François Côté, and which over the years has significantly improved our methods of prevention, diagnosis and treatment.
 
For over 20 years now, Jean-François Côté has been among those who contribute to this lifesaving scientific knowledge. A seasoned scientist, Jean-François Côté is the Vice-President, Research and Academic Affairs and the Director of the Cancer and Genetic Diseases Research Axis at the Montreal Clinical Research Institute (IRCM), where he conducts his research. He is also an Accredited Professor in the Department of Medicine at the Université de Montréal. From the beginning of his career, he has focused on a determinant of cancer mortality: metastases.
 
This term, now known to everyone and rightly feared by the general public, is often accompanied by a feeling of dread for people suffering with cancer and their loved ones. Metastases are cancer cells that travel from the main tumor to colonize other organs, in order to survive. When colonized sites turn out to be vital organs, the function of these organs is impaired, which often causes severe pain and, if left untreated, results in death. Therefore, the relevance of Jean-François Côté’s work speaks for itself, every time the word metastasis is spoken in a doctor’s office, or around a kitchen table.
 
For Jean-François Côté, this desire to understand more about the formation of metastases began during his doctorate at McGill University, under the supervision of renowned professor Michel L. Tremblay. He was interested in the molecules controlling cell mobility. Then, during his postdoctoral fellowship at the Sanford Burnham Prebys Medical Discovery Institute in California, he deepened his research aimed at identifying new molecular mechanisms by which cells move, with the idea that this could explain the formation of metastases. All this led him to make a discovery that revolutionized research in molecular and cellular biology: he identified a superfamily of 11 proteins, known as the DOCK proteins, which controls various aspects of cell mobility and is believed to be involved in several diseases. When he joined the IRCM in 2005 as Director of the Unit on Cytoskeletal Organization and Cell Migration, he incorporated in vivo models and analyses of samples from breast cancer patients into his work. This journey gave rise to an idea that he would implement at the IRCM: the creation of a research program aimed at better understanding cell mobility and invasion in order to identify therapeutic targets that could one day lead to anti-metastatic treatments. The idea became a passion.
 
Today, in light of the discoveries made in Jean-François Côté’s laboratory, there is hope for a better future. Recent advances have shown that a DOCK1 protein plays a central role in the formation of metastases. Extensive studies of the protein together with collaborators around the world have resulted in the creation of the first generation of pharmacological inhibitors against DOCK1. These inhibitors have been shown in the laboratory to be able to block metastases. The question is: will this work for humans?
 
At the same time, Jean-François Côté’s team also identified a molecule called AXL, which is believed to be implicated in an aggressive breast cancer: HER2 breast cancer. Recently published in the renowned journal Nature Communications, the study shed light on the prometastatic functions of AXL. While the ability of AXL to promote metastasis formation was already known, the underlying molecular mechanisms remained hitherto unclear. The team has developed an approach to study more than 700 proteins and their mechanisms, which when triggered by AXL, facilitate cell movement and therefore metastasis. By blocking the action of AXL with the help of pharmacological inhibitors, it therefore becomes possible to hinder the process of cell migration that is so badly needed by metastases. Among these proteins, the team identified PEAK. When the connections between AXL and PEAK1 are destroyed, tumors are unable to efficiently metastasize to other organs. This work sheds light on a substantial amount of new information on intracellular signaling controlled by AXL and positions the PEAK1 protein as a potential avenue for developing new anti-metastatic approaches.
 
After 20 years of hard work, Jean-François still has his passion from the early days, driven by a dream that remains relevant:  to one day help breast cancer patients fight metastasis and beat cancer. 
 
Every day, our researchers are discovering more about cancer, and every day, they are working together to improve outcomes for patients. In this breast cancer month, we salute Jean-François Côté and those like him who rekindle our hope for a future where cancer can no longer kill.
 
 

Source

Jean-François Côté
Interim President and Scientific Director of the IRCM; Vice President Research and Academic Affairs; Research Unit Director