How can oncologists predict which cancer treatment is most likely to work for a given patient? Dr. Andrew Freywald explores that question by growing tiny, living models of real-life patient tumours — organoids— then watching how each one responds to existing cancer drugs.

Freywald, a longtime cancer researcher and professor in the Department of Pathology and Laboratory Medicine at the University of Saskatchewan's College of Medicine, said establishing an organoid development protocol took a "lot of trial and error."

"This is a complex process. It requires a lot of factors and also requires a lot of technical expertise," said Freywald, crediting his laboratory team. He said it took several years to create the right conditions to grow miniature pancreatic and ovarian tumours.

Freywald and his team deliberately chose two of the most difficult cancers to treat. Only 13 per cent of patients diagnosed with pancreatic cancer survive five years.

In women, ovarian cancer causes more deaths than any other cancer.

"Both cancers need serious improvements in treatment protocols," said Freywald.

He said when first-line cancer therapies don't work, modeling tumours in organoids will allow researchers to narrow down the most efficient drugs.

"It was amazing for me how really closely these models represent the regional tumors in terms of their genomic organization and in terms of their morphology," Freywald said.

He said the challenge lies in the tumours themselves. Each one is slightly different from the next.

"This uniqueness makes it very hard for oncologists to predict which tumor, which treatments would or would not work."

Over the coming months, Freywald and his team will test organoids derived from 100 individual tumour samples, assessing them against thousands of approved drugs. Their research is still in the proof-of-principle stage; it isn't yet a routine way to choose a patient's treatment.

But if Freywald and his team succeed, this could help pave the way for clinical trials and more personalised cancer care.

"Our analysis would probably provide these options to them and that would obviously improve their chances for survival," Freywald said.

His research is supported by donations to Saskatoon's Bruce Gordon Memorial Pancreatic Cancer Research Fund, along with Genome Prairie, CIHI, the University of Saskatchewan, the Saskatchewan Health Research Foundation, and health start-up OncoForma.

"Our hope is that when we pass these through initial stages, including clinical trials, we will be able to convince Health Canada to accept it as a standard of care, at least for some cancers," said Freywald.

"It's really exciting."

Miniature human brains grown in a Saskatoon lab are upending the way researchers see neurology and immunology. Neuroscientist Dr. Tyler Wenzel is using brain organoids to challenge decades of rodent-based research, charting a new course for precision medicine.

As a high school biology teacher, Wenzel's students learned how hearts pump blood and lungs move air. But apart from neurological electrical activity, neither Wenzel nor the textbooks had many clear answers about the brain.

During his graduate studies, Wenzel realized the same experimental question tended to produce opposite results for mice and humans. The key difference, he found, lay in how each species' responded to toxins and injury, leaving him skeptical of neurological therapies tested on rodents.

Now an assistant professor of psychiatry at the University of Saskatchewan, Wenzel focuses on youth degenerative brain disease and the limits of traditional research models.

He grows human brain organoids — "mini brains" — from pluripotent stem cells derived from sources like blood or skin. Measuring two millimetres apiece, those organoids resemble tiny blobs of chewing gum.

"We will turn [cells from a patient] into pluripotent stem cells, and we will make their mini brain, and because it has their genetic information, we get a brain that has their pathology," Wenzel said.

"If you do that same mutation, often in a mouse, the pathology won't appear. So it allows us to actually get a pathology we can actually study," he said.

When Wenzel was first hired at the University of Saskatchewan in 2024, the budget-conscious researcher built his lab on a shoestring, picking up secondhand centrifuges, balances, fridges and freezers from industrial start-ups. That move saved him time, and hundreds of thousands of dollars.

"All the money that we started off with, it is literally going to just the research team and directly to the research," Wenzel said, crediting NSERC and SHRF for their support. "I am so grateful."

Today, Wenzel studies childhood cerebral X-linked adrenoleukodystrophy (ALD), a rare degenerative brain disease that strikes children, and is fatal when left untreated. His organoids may provide proof of concept for new ways to target the brain and nervous system, without the need for radiation, chemotherapy, and lifelong immunosuppresant drugs currently required for hematopoietic stem cell transplants.

"Chemotherapy and irradiation makes holes throughout your whole body. So we can do it in just your brain, just your spinal cord, and then we can inject the immune cells specifically into those locations," Wenzel said. "That eliminates many of the things that make chemotherapy uncomfortable, many of the things that make any sort of stem cell transplant uncomfortable."

This spring, Canada's Stem Cell Network singled out Wenzel's work with a Rising Star Award, saying his work demonstrates "leadership, creativity and potential for major impact".

If his method shows promise in treating ALD, Wenzel's approach could pave the way for more targeted, effective and far less invasive treatments for a range of degenerative brain diseases.

As Researchers Under the Scope marks its 100th episode, we hand the microphone to Dr. Linda Chelico, who recently accepted a five-year term as Vice-Dean Research, Biomedical Sciences, at the University of Saskatchewan's College of Medicine.

Originally from Melfort, Saskatchewan, the virologist and biochemist outlines her two main priorities: upgrading research infrastructure and raising the public profile of her colleagues' work.

Since the Covid-19 pandemic, Chelico said biomedical researchers are now expected to team up producing multiple lines of evidence supporting the same conclusion, before publications accept their findings.

"Is it just specific to that cell? What about cells from other parts of the body, or other cancers?" she explained. "They might also want you to do the studies in an animal model."

Alongside a second vice-dean who will oversee the College of Medicine's clinical trial unit, Chelico wants to strengthen collaboration, pushing more discoveries toward real-world treatments.

She also says it's time to make biomedical research more visible to donors and the general public, through social media outreach and real-life tours of the Health Sciences complex.

"A lot of times people drive by this nice, shiny building, this new building that went up, you know, 10 years ago, on College Drive and they probably wonder, what are we doing in here?"

Chelico said connecting those dots should help boost health-related infrastructure investment from both the public and private sectors.

A yet-unnamed vice-dean will focus on clinical health sciences and population health, overseeing the College's clinical trial service unit. Together, Chelico says their goal is to more effectively link laboratory discoveries with investigator-led clinical trials that lead to new treatments for real-life patients.

She sees this as a time for renewal.

"I think it's a really great time to be here as a biomedical researcher, because there's a really big chance to have an impact on what the future will be," she said.

"People are really collaborative here."