New weapons to fight bone marrow cancer


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Bone marrow cancer is a battle too many people still face. To outsmart the disease, Québec researchers are looking at genetic anomalies associated with its various forms and studying the defective proteins of cancer cells.


Acute myeloid leukemia (AML) is one tough disease to beat! Despite major efforts to get it under control, this rare cancer of the bone marrow cells remains extremely lethal: only 30% of adults recover completely. Guy Sauvageau, a researcher at the Institute for Research in Immunology and Cancer, and Josée Hébert, a researcher at Hôpital Maisonneuve-Rosemont, are encouraged by the prospects of saving more lives by studying the DNA and proteins of cancer cells to detect their weaknesses and tailor treatments accordingly.

Guy Sauvageau 

One disease, many faces


The two hematologists are waging war against acute myeloid leukemia. In 2009, they launched Leucegene, a project dedicated to developing accurate diagnostic and prognostic tests. “At the time, there was a severe lack of reliable tools to predict how the disease would progress and how well treatments would work,” says Dr. Sauvageau. Using the latest genome sequencing techniques, the researcher and his team have over time established a list of many genetic anomalies in order to better classify the different forms of AML. Leucegene has now become a global benchmark for the decoding of these anomalies and for their use as markers to determine the correct treatment for each form of the disease.

For instance, acute promyelocytic leukemia, a subtype of AML, is associated with a genetic anomaly considered to have favourable risk for patients. In other words, a cure is possible if using a therapy specifically tailored to the subtype. For high-risk cases of anomalies, however, patient survival is unfortunately less likely even with chemotherapy. Doctors then recommend bone marrow transplant. The two researchers and their team continue to refine the molecular classification of the many genetic variants of AML so that the response to different treatments can be better predicted.

cancer cells

Targeting the weak points of cancer cells


Dr. Sauvageau and his team have already tested 10,000 drug compounds for use on these genetic anomalies. The colossal task has helped to detect the weak points of cancer cells and identify the compounds most effective at fighting AML’s various forms. In fact, this is how they discovered that a drug primarily used to treat arthritis would make a great weapon in cases with an unfavourable prognosis.

Yet despite all the progress being made thanks to genomics, 30% of patients ranked as intermediate risk still do not have access to optimal treatment. “We want to bring this number down to 10% by using new genomic technologies to help us detect unknown genetic anomalies and, ultimately, develop new, more accurate diagnostic and prognostic tests to improve treatments for these patients,” explains Dr. Sauvageau.

 

Are proteins the answer?


While certain drugs do a great job at treating the various forms of AML by attacking their weak points, Dr. Sauvageau is convinced that we need to look beyond genes: “We need to find the protein that is not working or not working properly in the cancer cell because of the anomaly so we can target it specifically with the right drug.” It’s a painstaking task that he and his team will carry out using a bank of leukemia cells developed in Québec by Dr. Hébert some 20 years ago.

In an effort to share the fruits of their labour, Dr. Sauvageau and Dr. Hébert will be publishing their findings on a public Web portal. “We want to support other researchers in their work and make the information available to patients and doctors. That way, a patient’s genetic anomalies can be identified and used by a specialist to try to predict the response to a drug,” explains Dr. Sauvageau. His research team is currently looking at guidelines to ensure the portal is used in a way that meets ethical and legal standards.

“In a few years, we hope to be able to tell our patients that based on the genetic anomalies of their cancer cells, they have a 95% chance of responding well to a given treatment selected according to their profile,” concludes Dr. Sauvageau. Now that’s personalized medicine at its best! 

 

Beyond genes: proteins


Thanks to advances in technology and a better understanding of the genome, the study of the proteome has grown exponentially. The proteome is the entire set of proteins produced by the cells of an organism. Proteins are the gene’s worker molecules. They ensure an organism’s proper functioning.

Given that the 20,000 to 25,000 genes produce thousands of proteins, the proteome is much bigger than the genome. Proteomics, which is to proteins what genetics is to genes, promises to unlock many hidden secrets leading to the development of new drugs.

Guy Sauvageau

“In a few years, we hope to be able to tell our patients that based on the genetic anomalies of their cancer cells, they have a 95% chance of responding well to a given treatment selected according to their profile.” 


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