A made-in-Canada tool to fight cancer

New Frontiers in Research Fund | Published: 2023-08-03 10:00 AM (eastern)

A Canadian research team that stretches from BC to Quebec is developing a new way to treat late-stage cancers. The project, called Rare Isotopes to Transform Cancer Therapy, will be supported over the next six years by a New Frontiers in Research Fund Transformation grant worth nearly $24 million.

“It gives us the funding and the resources we need to make sure that we can actually see this to fruition,” says the project’s nominated principal investigator, François Bénard. The radiology professor is also associate dean at The University of British Columbia’s faculty of medicine, and senior executive director of the BC Cancer Research Institute.

“It will really help move the dial,” he says.

The project aims to harness the power of nuclear medicine to introduce new candidate drugs for treating specific cancers, including prostate, pancreatic, breast and blood cancers. A talented multidisciplinary team that includes nuclear physicists, nuclear engineers, chemists, biologists and oncologists will use radioactive isotopes (atoms that contain an unstable combination of neutrons and protons) to develop a “holy grail” of cancer treatment.

Research into new treatments is particularly relevant and urgent in Canada, where cancer is the leading cause of death. Worldwide, the number one killer is heart disease, but Canada’s aging population means more and more people are being diagnosed with cancer: nearly one in two Canadians are diagnosed with cancer during their lifetime, and one in four will die from the disease. Survival rates are improving for early-stage cancers, but mortality rates remain stubbornly high for later-stage cancers.

Radioactive isotopes offer new hope for people whose cancer has metastasized. Cancerous growths are sensitive to damage by radiation. By injecting patients with very small amounts of radioactive isotopes attached to designer molecules, it’s possible to deliver an effective treatment aimed directly at the cancer cells. A prime example is Actinium-225 (Ac-225). In a 2015 German case that went on to attract global attention, a man in his 70s who had terminal prostate cancer, and had exhausted all other treatment options, was given a promising but untested Ac-225 drug. He went into full remission.

Bénard describes targeted radiopharmaceuticals as smart drugs—they circulate in the blood until they encounter cancer cells, to which they stick very tightly, causing rapid accumulation of the radioactive drug at tumour sites. This allows them to deliver radiation very precisely at multiple sites across the body, killing cancer cells, while doing little harm to the healthy tissues nearby. That makes this treatment more precise than radiation and chemotherapy, the main ways of fighting cancer.

The challenge for both researching and using the isotope is how rare it is. It’s sourced from the remnants of the production of atomic weapons in the 1950s and 1960s. Globally, the naturally occurring supply of Ac-225 is equivalent to just a few grains of sand—about enough to treat 2,000 patients a year.

Enter the project’s co-principal investigator. Caterina Ramogida is an assistant professor of chemistry at Simon Fraser University, jointly appointed to TRIUMF, Canada’s nuclear particle accelerator centre. One of Ramogida’s projects while she was a postdoctoral researcher at TRIUMF was to figure out how to make Ac-225.

“We did it using a different way than we’re doing now,” she says. “But we were able to make small amounts that we could do a bit of research with.”

Now, Ramogida will be applying her chemistry expertise to guide the research team in designing the best way to connect each isotope to its disease-targeting molecule and ensure its safe transport through the body. It’s a step that is critical for developing drugs able to target multiple types of cancer.

TRIUMF will be home base for the production side of the isotopes project. But since Ramogida’s early days, the production goal has expanded exponentially. The researchers want to produce enough Ac-225 for Canada to become the world supplier for the anticipated surge in global demand.

Throughout the research process, the team’s social scientists will provide feedback on how patients and clinicians are likely to react to the new type of treatment. It’s a unique part of the project’s set-up, encouraged by the transdisciplinary requirements of the Transformation stream. Ramogida thinks it will, ultimately, make the project more successful.

“As a researcher, I have my perspective of what I think, scientifically, might be a good idea,” she says. “But having that perspective from the social scientists, getting insight from the patient and clinician perspective, is really cool for us and will help us with smarter choices of what we invest our time researching.”

Bénard is optimistic that the research will significantly improve the quality of life and life expectancy of patients with metastatic cancers.

“It has, I think, struck the imagination of many of us that it is feasible to use this to get really, really deep responses and improve the care of cancer patients,” Bénard says. “We really want to work together to boost Canada's capacity in developing those drugs, and also developing domestic isotope production capacity.”