Endometrial cancer is the most common gynecological cancer and one of the most common cancers in women globally. Terry Fox-funded researchers with the Gynecologic Cancer Initiative (GCI), led by surgeon-scientist Dr. Jessica McAlpine, helped transform endometrial cancer care through the development and validation of a molecular classification system that stratifies patients by their risk of recurrence. Building on this, researchers are now working to address the next set of challenges, including reliably predicting when or why some patients develop endometrial cancer, which treatment(s) are most effective for different molecular subtypes, and why some patients have innate or acquired resistance to treatment.
With $9 million in renewed funding from a Terry Fox New Frontiers Program Projects Grant (PPG), this GCI team will try to answer these questions and develop more precise approaches for early detection and prevention, new treatments, ways of predicting treatment resistance and toxicities, and non-invasive methods of monitoring treatment response and tumour evolution over time. Taken together, this project aims to improve outcomes for patients with endometrial carcinomas while reducing disparities in care.
“There is an urgent need for more precise care in endometrial cancer allowing us to identify who can safely avoid additional treatment after surgery, who needs more intensive therapy, and how to deliver the most effective treatment with the fewest side-effects, including sparing fertility,” says Dr. Jessica McAlpine, project lead, surgeon-scientist at Vancouver General Hospital and BC Cancer, and professor at the University of British Columbia (UBC).
“In this project we want to continue transforming care by understanding endometrial cancer from all angles—from first development through advanced metastatic disease.”
Over the next five years, this team will investigate how these cancers develop—progressing from benign endometrium to precancer and eventually cancer—with the goal of identifying opportunities to intervene earlier and preventing cancers from developing or detecting and treating them at their earliest stage. This part of the program is co-led by Dr. McAlpine and Dr. Ali Bashashati, an associate professor at UBC and scientist at the GCI.
At the other end of the spectrum, the team will evaluate promising new treatments in laboratory models for the 30 per cent of endometrial cancers with the poorest outcomes and highest risk of recurrence. This part of the program is co-led by Dr. David Huntsman, professor at UBC and scientist at the GCI, and Dr. Dawn Cochrane, adjunct professor in the Department of Obstetrics and Gynecology and scientist at the GCI. Their work will focus on emerging therapeutic approaches that target specific proteins on the surface of cancer cells. These studies could lay the groundwork for future clinical trials and more precise treatment approaches tailored to the biology of each patient’s cancer.
The team is also investigating why some patients respond well to immune checkpoint inhibitors, a highly impactful new category of immunotherapy that reinvigorates the immune system’s ability to recognize and attack cancer, while others experience severe side-effects with without therapeutic benefit. As immunotherapy becomes more widely used for advanced and recurrent endometrial cancers, the team aims to identify reliable biomarkers that can predict both treatment response and toxicity. This part of the program is co-led by Dr. Kelly McNagny, professor in the School of Biomedical Engineering and Department of Medical Genetics, and Dr. Allen Zhang, gynecologic pathologist and scientist at GCI.
Finally, the team will use non-invasive tools to monitor patients during treatment and track how tumours change over time, helping to explain why some cancers spread while others do not. These tools may help detect recurrence of the cancer earlier, and guide decisions on what the next best treatment option may be for that individual. This part of the program is co-led by Dr. Andrew Roth, senior scientist at BC Cancer and associate professor at UBC, and Dr. Amy Jamieson, surgeon-scientist at GCI and assistant professor in the Department of Obstetrics and Gynaecology.
Together, this work will continue to guide endometrial cancer care across Canada and globally, ensuring patients have the best chance of receiving the right treatment at the right time.
“Our first Terry Fox New Frontiers Program Project Grant has already improved patient care, changing clinical guidelines internationally. Donors to the Terry Fox Foundation made that possible,” says Dr. McAlpine. “We’re extremely grateful to the Terry Fox Research Institute for this renewed support, enabling us to translate research into clinical care and advance precision medicine for patients with this very common and difficult-to-treat cancer.”