USask researchers target prostate cancer cells to develop new treatments

A collaborative research team led by Drs. Franco Vizeacoumar (PhD) and Andrew Freywald (PhD), received $983,026 in funding from the Canadian Institutes of Health Research (CIHR) for their project: Identification of therapeutically relevant targets in telomerase overexpressing prostate cancers. This project was ranked as No.1 in the CIHR grant review panel. Their team also includes two researchers at the University of British Columbia, Drs. Judy Wong (PhD) and Yuzhuo Wang (PhD).

While therapeutics exist to help patients with prostate cancer, there is a limited degree of effectiveness. Many individuals develop resistance to the available drugs and the treatments are no longer successful.

Through their research, the team aims to identify molecules within prostate cancer cells that can be targeted with existing or novel drugs to improve treatment efficiency.

“The resistant patients are going to die, so we need to find a new way to treat them. That’s why we hope our strategy would be helpful and a lot of these patients will be saved,” said Freywald, who along with Vizeacoumar are the primary investigators on the project, and professors in the College of Medicine’s Department of Pathology and Lab Medicine. 

The team aims to identify therapeutically relevant targets in the context of the overexpression of an enzyme called telomerase. Humans have the genetic coding necessary to produce telomerase, but only cancer cells produce it. Cancer cells require telomerase to grow indefinitely and eventually form a tumour.

“The approach that we are actually trying to use is based on telomerase overexpression and will affect all tumor cells and prostate tumours, since this enzyme is overexpressed in practically all subtypes of prostate cancer,” said Vizeacoumar. 

Vizeacoumar and Freywald are looking for targets that inhibit telomerase overexpressing cancer cells, eliminate them and block tumour growth while not affecting normal healthy cells. Doing this could potentially reduce the spread of cancer within the body.

The researchers find these targets by “turning off” each gene in the genome (approximately 20,000 genes total) and searching for the genes. By doing this, the activity of only the telomerase-positive cells is inhibited. This will allow the team to identify the most effective therapeutic targets.

The team uses the CRISPR gene editing technology to achieve this.

“We go and turn off every single gene and then ask if telomerase expressing cells are dependent on them. We do that for every single gene in the genome and we pick up the most promising potential targets,” explained Vizeacoumar.

The pair also see possibilities for this type of treatment in other types of cancer.

“All cancers have this feature of overexpressing telomerase. Some of the targets that we find in this research will be also applicable in multiple other cancers and how will that help,” said Vizeacoumar.

Vizeacoumar sees their research as the initial step to further development in cancer therapies. 

“It's up to clinical trials after this to figure out how effective the real life treatment is,” he said. “I think it's going to be applicable to the broad spectrum of human cancers that are out there. At some point down the road, we're also thinking about combining this with some of the existing therapies and see if we can actually make it better.”