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.
