2021 Scientific Discovery Award Quebec Science is awarded to the team of Jean-Jacques Lebrun at RI-MUHC for identifying the genetic mechanisms at work in triple negative breast cancer and discovering a promising targeted polytherapy.
29 years magazine Quebec Science continues the tradition: each fall, a jury of researchers and journalists selects the 10 most impressive Quebec discoveries of the past year, and then the public is invited to vote for one of them. This year, it was the discovery that made it possible to update the genetic mechanisms operating in aggressive, so-called triple negative breast cancer, and the discovery of a promising new method of treatment that won the favor of readers as part of the discovery. competition 2021.
Every day, 75 Canadian women are diagnosed with breast cancer and 15 die from it. To date, there is no targeted treatment for the most aggressive form of the disease, but thanks to the discovery of the team of Jean-Jacques Lebrun, MSc, PhD, Research Associate at the McGill University Health Center Institute (RI-MUHC), things could change.
What if we start from scratch?
It’s a bit like what Jean-Jacques Lebrun told himself when he was battling “triple negative” breast cancer, one of the most aggressive forms of the disease. It accounts for about 15% of cases, but it is responsible for half of the deaths. “The only treatments are chemotherapy and radiation therapy, which don’t work well. The risk of metastases and recurrences is high,” explains the researcher.
To find the Achilles’ heel of these tumors, his team combed their entire genome to find genes that play a predominant role in the tumor process. The team cultured cancer cells from triple-negative breast cancer patients in the lab and “turned off” their 20,000 genes one by one using CRISPR-Cas9 technology, a kind of “genetic scissors”. These cancer cells were then transplanted into the mammary glands of mice. As they multiplied, the researchers were able to determine the ability of each gene to slow down or block tumor development.
The team identified two main signaling pathways, that is, two “networks” of genes that change the behavior of cells. One of them, the mTOR pathway, is known to be unregulated in some cancers and promote uncontrolled proliferation. The other, the Hippotropic pathway, in contrast, is a protective pathway: at normal times, it protects cells from tumor slippage.
The researchers then tested drugs that could target these pathways and found two effective ones: torin 1, a second-generation drug known to block the mTOR pathway, and verteporfin, a drug commonly used for retinal disorders that can activate the hippopotamus pathway. . After testing them on cancer cells from hundreds of patients suffering from various triple-negative cancer subtypes, the researchers found that the two drugs, administered together, had an effect greater than the sum of their individual effects and were able to destroy the tumor.
Published in NatureCommunication, these results are the fruit of five years of hard work. The next step will be the organization of clinical trials, which Mr. Lebrun is working on.
“Cancer affects all of us in one way or another, and every year we notice that readers are sensitive to advances in oncology. This discovery is encouraging because it comes with concrete hope for a cure,” comments Marin Korniu, journalist and deputy editor-in-chief. Quebec Science.
“I am honored to receive this public discovery award in the field of basic research. To date, very few studies have used CRISPR genome-wide genetic screening in vivo, and our study highlights the power and reliability of this technology for identifying innovative and clinically relevant therapies in the field of cancer. We know that many drugs fail at the clinical stage, but I am optimistic because we started with a mechanism to find a concrete solution,” said Jean-Jacques Lebrun, Senior Researcher at the Cancer Research Program at the Institute. McGill University Medical Center and professor of medicine at McGill University.
“On behalf of the entire McGill University Medical Center Research Institute community, I would like to congratulate Dr. Lebrun and his team on this encouraging discovery. We are proud to be able to offer researchers like Dr. Lebrun an environment that integrates biomedical research and clinical medicine. “As the largest research institute in Quebec, RI-MUHC is accelerating the application of fundamental public health discoveries, thereby contributing to better health for children and adults throughout their lives,” says Dr. Rian Toyse, Executive Director and Chief Scientist employee of NII-MUVK.
Also in attendance were Meiu Dai, Gan Yang, Ni Wang, Girija Dahlia, Sophie Poulet, Julien Boudreau and Suhad Ali (McGill University Medical Center Research Institute), and Ashlyn M. Edik and Sergio A. Burgos (McGill University). ).