Study offers hope of a new treatment for rare endometrial cancer | Folio

Study offers hope of a new treatment for rare endometrial cancer

Drug used for heart disease could have an anti-cancer role after unexpected findings.

September 16, 2024 By Keri Sweetman

Digoxin, a drug used to treat heart failure, shows promise for treating a rare but aggressive form of endometrial cancer that can't be treated with the current chemotherapy drug. (Photo: Getty Images)

A team of researchers at the University of Alberta has found that digoxin, a drug widely used to treat congestive heart failure, is an effective therapy for a rare and aggressive form of endometrial cancer.

The findings, published in the July issue of the journal Gynecologic Oncology, were a surprise to the researchers, says Cheng-Han Lee, associate professor in the Department of Laboratory Medicine & Pathology and Sawin-Baldwin Chair in Ovarian Cancer.

"People had begun to uncover the anti-cancer role of digoxin about a decade and a half ago," says Lee, who was senior author on the study. "But they never figured out why it seemed to work on some cancers and not others, so it was difficult to translate the findings to clinical practice."

The new U of A study, which was the master's thesis of graduate student Pooja Praveen Kumar, involved collaboration with scientists at the University of Saskatchewan and the University of British Columbia. The researchers used surgical tissue samples from patients with a highly aggressive type of endometrial cancer to create three-dimensional laboratory cell models that closely resembled how cancer cells would behave in humans.

They tested hundreds of drug compounds that might work to control the endometrial cancer cells, using a robotic platform at the Saskatchewan Cancer Agency.

Digoxin was identified as a promising drug candidate, along with several other drugs in the cardiac glycoside compound family. The findings are critical because the current chemotherapy drug widely used for endometrial cancer doesn't work on this highly aggressive subset, known as dedifferentiated endometrial carcinoma (DDEC).

Endometrial cancer affects thousands of Canadian women

Endometrial cancer is found in the inner lining of the uterus and is the most common gynecological cancer in Canada, according to the Society of Gynecologic Oncology of Canada. An estimated 8,600 Canadian women will be diagnosed with uterine cancer this year, more than 90 per cent of which are endometrial.

Though the five-year survival rate for most endometrial cancer is as high as 90 per cent if the disease is found early, the prognosis for women with the DDEC subset is dire. Although it makes up only about two per cent of endometrial cancers, the 100 per cent mortality rate means finding a treatment is crucial.

"With a lot of cancer we study, we plot the median survival in years," says Lee. "With this one, it's only three or four months median survival. So it's terrible."

Lee, who received his MD-PhD degree and his pathology residency training at the University of British Columbia, started studying this rare cancer in 2013 during an earlier stint at the U of A, working with the previous Sawin-Baldwin Chair, Lynne Postovit. They used next-generation genetic sequencing technology to understand the unique molecular biology of these tumours that could explain why they kill patients so quickly.

That research provided the foundation for the new study. The researchers expect to present their findings to clinical trial groups in Canada and the United States, with the hope that an organization might consider using digoxin on patients in a trial. But that process could take years, Lee stresses.

Followup project starts in September

The immediate next step for Lee's team is a two-year project, funded by the Cancer Research Society, to understand the mechanism by which digoxin kills the aggressive DDEC cancer cells.

"It's almost like we are repurposing this drug because it has an unexpected anti-cancer effect against this cancer," Lee says. "If we understand how these cancer cells are vulnerable to the drug, then we can ask the question: is there a more specific way to target this?"

Lee is also curious to know whether there could be other drugs that would be even more effective than digoxin, or whether digoxin could be combined with another drug to make it better tolerated. One possibility would be looking at combining digoxin with doxorubicin, already used as a second- or third-line treatment for endometrial cancer.

The research could have broader implications beyond this rare type of endometrial cancer, adds Lee, who is a member of the Women and Children's Health Research Institute and the Cancer Research Institute of Northern Alberta.

"I'm optimistic that through studying the mechanisms involved in why this endometrial cancer is vulnerable to this drug, we will be able to learn more about how to treat other aggressive cancer types."

The Sawin-Baldwin Chair in Ovarian Cancer is supported by the Alberta Women's Health Foundation and the Alberta Cancer Foundation.

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