In 2023, Paul Lonergan spent months trying to find out the cause of his never-ending sore throat. After going back and forth between doctors, the Toronto resident eventually got a shocking diagnosis: he had a large tumour at the base of his tongue.
“I realized I had a fight on my hands,” the 63-year-old said.
Lonergan endured seven weeks of radiation, alongside chemotherapy — a gruelling set of treatments that put him in and out of the intensive care unit — in order to destroy all signs of his tumour.
But was his cancer actually cured?
Through a clinical trial offered by his medical team, Lonergan received a “liquid biopsy” to find out. The relatively new approach to cancer detection uses simple blood tests to spot traces of tumour DNA that can’t be seen in traditional scans and exams. In Lonergan’s case, the testing showed he still had tumour fragments flowing through his blood, suggesting his successfully-treated tongue cancer could eventually come back.
Lonergan was offered experimental immunotherapy and has since been cancer-free, according to later rounds of liquid biopsies that scoured his bloodstream for the tiniest traces of the disease.
Few Canadians have access to this emerging form of cancer monitoring, which is still largely confined to the world of clinical trials or pricey private clinics. But there’s growing hope that this could change.
Dr. Ramy Saleh, a cancer researcher and medical oncologist at the McGill University Health Centre in Montreal, said the approach has the potential to “revolutionize” how clinicians watch for disease recurrence.
“I think the challenge with liquid biopsies,” he said, “is we’re just discovering the tip of the iceberg.”
Now, a Toronto-based team is launching a massive, years-long research project to figure out how to use this emerging technology in routine patient care — with a goal of finding better ways to protect cancer survivors from having the disease come back, while sparing some from enduring costly, invasive treatments.
5-year clinical trial underway
Led by scientists from the University Health Network (UHN) in Toronto, the clinical trial will offer liquid biopsies to more than 7,000 patients — individuals who’ve already gone through traditional “curative” treatments for various types of cancer — over the next five years.
“What we are trying to do is to see whether these sensitive tests can detect circulating tumor DNA that would suggest that the cancer may have a possibility of returning and relapsing,” said study lead Dr. Lillian Siu, a senior scientist at UHN’s Princess Margaret Cancer Centre and a scientific lead at the Peter Gilgan Centre for Early Cancer Detection Research.
Since it’s all about the detective work to find hidden signals of disease, Siu’s team dubbed the project SHERLOCK, short for a “Study of High-Precision Evaluation of Molecular ResiduaL Disease Through a PlatfOrm for Cancer TracKing and Interception.”
“What SHERLOCK is trying to do is to take it one step earlier, that before we can see [cancer] on a routine clinical exam or CT scan, we can actually detect it in the blood first,” Siu said.
“And the hope, obviously, is when you detect it so early, we can do something about it earlier, and hopefully offer these patients a better chance at receiving curative treatment.”
In cases where researchers spot early warning signs in a study participant, the team will link them with other clinical trials offering access to next-generation treatments.
That could mean experimental immunotherapy, newly-designed drugs, or even buzzed-about GLP-1s — the family of weight loss and diabetes medications that includes Ozempic — to see if additional treatment can wipe out their cancer completely.
But it’s not just about offering experimental treatments. In some cases, it’s about avoiding heavy-duty medical care entirely.
Siu stressed that her team’s second goal is to figure out how liquid biopsies could be used to help some patients skip extensive, life-altering treatments “if there is no evidence of residual disease present in the blood.”
Decade-old technology
Understanding how well liquid biopsies work for cancer survivors, and whether they can truly guide follow-up care, will take far longer than any single clinical trial.
Siu says there’s still much to learn about this technology, given how new it is.
These tests have only been available for a little more than a decade — the term “liquid biopsy” was only coined in 2010, with the first option approved by the U.S. Food and Drug Administration a few years later — and initially required large amounts of fluid. (Usually, that means blood, but it can also include other bodily fluids such as cerebrospinal fluid, the watery liquid surrounding the brain and spinal cord.)
In recent years, however, the technology started to improve, allowing for more typical amounts of blood to be drawn for each test, opening up new avenues for cancer monitoring.
“Now we have what we call ‘ultra-sensitive technology’ that allows us to find molecules of DNA in the blood, which we previously did not have the ability to detect,” Siu said.
There’s now a growing body of research already suggesting liquid biopsies might be a powerful tool for detecting residual disease after cancer surgery, while other studies show links between catching tumour fragments early and those patients experiencing longer survival times, or a lower risk of disease progression, for several types of cancer.
This technology is already in use as a diagnostic tool in at least one Ontario hospital, and was announced as a new option to monitor lung cancer patients in New Brunswick in 2024.
A liquid biopsy, which involves a blood sample, is less invasive than a tissue biopsy for patients undergoing treatment, says Health Minister Bruce Fitch.
‘Early days’ for this technology
Dr. Christopher Booth, a medical oncologist and health services researcher at Queen’s University in Kingston, Ont., says liquid biopsy use for cancer survivors raises some thorny ethical issues.
“If you’re in remission for colon cancer or breast cancer, and you’re feeling good, your CAT scans are clear, would you want your doctor to tell you that you might have cancer cells floating around in your body? Would you want to know that?”
While Booth stresses this kind of screening method may take a “psychological and emotional toll” on some patients, he says others do want to know and act early, and he praised the UHN team for tackling how to best use this emerging technology.
What’s already clear is these tests aren’t perfect, Booth said. Liquid biopsies can produce both false positives — cases where a patient can be told there’s some cancer DNA floating in their bloodstream, but they actually don’t have cancer — and false negatives, where the test shows they’re cancer-free, though the disease is brewing somewhere in their body, he explained.
“Some people would want to know because they can plan their life accordingly. Other patients might not want to know,” he said. “And then you add on top of that the possibility of a false negative or a false positive test, and there can be significant emotional burden.”
A private clinic in Toronto is the first in Canada to offer a new cancer screening blood test called Galleri, but questions remain about the effectiveness of the $2,100 test.
Multiple experts also stressed these aren’t simply one-and-done tests. To catch cancer early, you would need to repeat blood work at regular intervals, but knowing the ideal method for various types of cancer requires ongoing study.
One liquid biopsy tool designed to screen for over 50 types of cancer, Grail’s Galleri test, failed to meet its main objective in a landmark U.K. clinical trial, researchers revealed earlier this year. The long-awaited results confirmed the test failed to meet a key trial endpoint of a significant reduction in Stage 3 to Stage 4 cancer, dashing hopes that the country’s health officials would invest in the technology for patient care.
Even so, some private clinics are already marketing tests like Galleri for early screening to people who’ve never had cancer, including here in Canada — with a price tag of roughly $2,000 or more. (The test isn’t actually approved by health regulators in either Canada or the U.S.; in this country, Health Canada doesn’t actually regulate privately-developed lab offerings.)
That’s prompting some concern that the hype around this novel testing approach is outpacing scientific evidence.
“There’s a lot of work to be done in this space,” Booth stressed. “This is certainly an exciting technology; it might have a really important role in cancer care … but it’s early days.”
Hope is to make tests routine, despite costs
The good news, Saleh said, is that the number of clinical trials being conducted around the world has quadrupled in recent years.
“Which means there’s a lot of excitement about this technology,” he said. “Our challenge in Canada is trying to see how the [public system] can pay or cover those costs.”
Saleh himself is studying how to use liquid biopsies for patients battling bladder cancer.
“I tell them: It’s not only one time. We have to do it every three to four months to make sure that you’re OK, but some of those tests cost in the $5,000 range, so it’s not something that you can easily absorb as a cost as a patient.”
The hope, Saleh says, is that projects such as UHN’s clinical trial offer clear evidence that liquid biopsies will actually save the health-care system money while improving quality of life for many patients.
“It’s going to be a game changer on that end,” Saleh predicted.
Siu, who’s leading the UHN research, is optimistic that her team’s trial — set to wrap in 2031 — will offer new insights into the vast potential for liquid biopsies in cancer care, in Canada and beyond.
“If we can provide that kind of data,” she said, “this test will become routine, and that can benefit a large number of patients.”
