UNIVERSITY OF OTTAWA RESEARCHERS UNCOVER HOW MODIFYING CANCER CELLS’S ENERGY SOURCES COULD LIMIT THEIR DEADLY SPREAD
Under the direction of Dr. Julie St-Pierre, a research team at the University of Ottawa is developing novel strategies to address metastasis (the spread of cancer cells to other body parts) — and the deadliest aspect of breast cancer.
Targeting mitochondrial dynamics—the ways that mitochondria alter their structure within cells—could be crucial in stopping the development of cancer, according to research just published in Science Advances on Nov. 7, by Dr. St-Pierre and her colleagues. For the millions of people impacted by breast cancer every year, this research symbolizes a ray of hope.
Cancer’s Weak Spot
While mitochondria are best known as the powerhouses of the cell, their role extends far beyond energy production. Dr. St-Pierre’s team studied how mitochondria influence cancer cell behaviour through ongoing cycles of fusion (joining together) and fission (splitting apart).
According to the study, which was co-led by Dr. Mireille Khacho at the University of Ottawa and Dr. Peter Siegel at McGill University, breast cancer cells with longer, more elongated mitochondria were much less likely to spread than those with fragmented mitochondria, implying that encouraging mitochondrial elongation may be a favourable way to slow the lethal progression of breast cancer.
The Power of Mitochondria
The team created strategies to increase mitochondrial elongation in metastatic breast cancer cells in order to better understand how mitochondrial shape influences the spread of cancer. By deleting certain mitochondrial fission proteins through genetic alteration, they were able to stop mitochondria from breaking apart and lower the likelihood that the cells would spread. Slower development and decreased survival and motility—two characteristics necessary for the cells to spread throughout the body—were displayed by the modified cells.
As Dr. Lucía Minarrieta, the study’s first author and a postdoctoral fellow at the University of Ottawa’s Faculty of Medicine, explained, “When we analyzed the mitochondrial morphology of different breast cancer cell lines, we observed that those with lower metastatic potential tend to have longer mitochondria. This suggests that a fragmented mitochondrial network could be associated with more aggressive presentations of the disease.”
Old Drugs, New Purpose
Amazingly, the team discovered that leflunomide, a medication that has already received Food and Drug Administration and Health Canada approval, could be a viable option to prevent metastasis since it can encourage mitochondrial elongation.
Leflunomide, which is now used to treat rheumatoid arthritis, has been found to successfully encourage mitochondrial fusion in breast cancer cells. Preliminary laboratory studies have also shown that it may be able to slow the development of cancer in animal models.
“We believe that promoting mitochondrial elongation in breast cancer cells could be used during the initial course of treatment to prevent metastatic recurrence in the long run,” said Dr. St-Pierre, professor in the faculty of medicine and University of Ottawa’s interim vice-president of research and innovation.
Toward a Future with Fewer Metastases
In order to ascertain whether leflunomide and related substances can successfully stop metastases in humans, Dr. St-Pierre and her team plan to further investigate their results in clinical studies. The goal of this research is to change the tide against breast cancer, which still claims thousands of lives every year, by developing a revolutionary treatment strategy.
In a world where breast cancer is still the most common disease diagnosed in women worldwide, this breakthrough is opening the possibility of novel, less invasive therapies that target the cellular level.
