Attacking cancer cells from the inside out

Researchers from the University of Toronto (U of T) are harnessing the power of proteins to stop cancer cells in their tracks.

“Proteins are the workhorses of the cell,” said Walid A. Houry, professor of biochemistry at U of T. “They define the cell and allow it to divide or migrate if needed.”

The team is especially interested in proteases, enzymes that chew up old or misfolded proteins and act as cellular quality control. Houry and his colleagues used the CMCF beamline at the Canadian Light Source (CLS) at the University of Saskatchewan to identify key compounds affecting these quality control mechanisms that cause cell dysfunction and, ultimately, cell death. Their research paper was recently published in Structure.

“Let’s say you have a small puppy and when you leave it in the room, it starts chewing your sofa, your carpet; it’s just hyper and eating everything up,” Houry said. The compounds cause the proteases to act like the puppy, “and the cell cannot handle this type of disruption to its machinery.”

By targeting the cell’s self-destruct button, Houry’s team, including collaborators at Madera Therapeutics, is designing a new approach to cancer therapy. Synchrotron techniques allowed the researchers to visualize the interaction between their compounds and the proteases.

Houry said hard-to-treat cancers like glioblastomas and certain types of breast cancers are good candidates for this new approach.

“Instead of inhibiting a protease, we are hyperactivating the protease, and that is unique.”

The CLS is crucial to the team’s work.

“Synchrotron technology is extremely important for us and our structure-based drug design,” he said. “We want to know why the protein is going wild when we add our compound.”

Read more on the CLS website

Image: Houry research team

Understanding how a key antibody targets cancer cells

Immunotherapy can be used as a precise intervention in cancer treatments. Jean-Philippe Julien is a Canada Research Chair in Structural Immunology, a Senior Scientist in the Molecular Medicine Program at The Hospital for Sick Children (SickKids), and an Associate Professor in the Departments of Biochemistry and Immunology at the University of Toronto. Along with colleagues from the U.S., Spain and Canada, he used the Canadian Light Source at the University of Saskatchewan to study how a candidate antibody therapeutic interacts with a surface receptor on cancer cells, which provides important molecular insights for designing improved cancer therapies. He mentioned how the synchrotron is “incredibly important for researchers like myself” and how “we cannot do the research that we do without it.” The team used the CMCF beamline at the CLS and their findings were published in the Journal of Biological Chemistry.Immunotherapy can be used as a precise intervention in cancer treatments. Jean-Philippe Julien is a Canada Research Chair in Structural Immunology, a Senior Scientist in the Molecular Medicine Program at The Hospital for Sick Children (SickKids), and an Associate Professor in the Departments of Biochemistry and Immunology at the University of Toronto. Along with colleagues from the U.S., Spain and Canada, he used the Canadian Light Source at the University of Saskatchewan to study how a candidate antibody therapeutic interacts with a surface receptor on cancer cells, which provides important molecular insights for designing improved cancer therapies. He mentioned how the synchrotron is “incredibly important for researchers like myself” and how “we cannot do the research that we do without it.” The team used the CMCF beamline at the CLS and their findings were published in the Journal of Biological Chemistry.

Learn more on the CLS website

Image: Jean-Philippe Julien

Credit: Canadian Light Source