Study Makes New Insights into the Origins of Ovarian Cancer

Pittsburgh, Pennsylvania, USA — Researchers at the University of Pittsburgh have identified a novel trigger of a deadly form of ovarian cancer: a subset of progenitor cells that reside in fallopian tube supportive tissue, or stroma.

The discovery of these high-risk cells are described in a new study published in March 2025 in Cancer Discovery, a journal of the American Association for Cancer Research. The study could pave the way for better approaches to prevent and detect high-grade serous ovarian cancer (HGSOC), the most common form of ovarian cancer.

“Ovarian cancer is the leading cause of death from gynecologic cancer in the Western world, but we currently have no way to detect it early and no prevention strategies apart from surgical castration, which is only indicated in high-risk women,” said co-senior author Lan Coffman, M.D., Ph.D., associate professor of malignant hematology and medical oncology in the Pitt School of Medicine and member of Magee-Womens Research Institute and UPMC Hillman Cancer Center. “Understanding the underlying biology of how ovarian cancer forms is critical to improving outcomes for our patients.”

HGSOC begins in the fallopian tubes when healthy epithelial cells transform into precursor lesions known as serous tubal intraepithelial carcinoma (STIC). Similar to how precancerous colon polyps can become colorectal cancer, STIC lesions often develop into HGSOC tumors.

But why do healthy cells become STIC? To find out, Coffman and her team turned to the stroma, the non-cancerous connective tissue that helps cancer grow.

“Most researchers have been focused on the epithelial cells that turn into these STIC lesions and eventually into cancer,” said Coffman. “Until now, no one has really looked at the surrounding stromal microenvironment of these lesions.”

In the stroma of ovarian cancer, a type of progenitor cell normally involved in growth and repair of healthy tissue — mesenchymal stem cells (MSCs) — become reprogrammed by tumor cells to support cancer growth. Coffman started by asking when these cancer-associated MSCs form and how early they play a role in cancer formation.

When she and her team profiled MSCs in the fallopian tubes of patients who did not have cancer, they were surprised to find cells that looked like cancer-associated MSCs in these healthy women. These cells, which the researchers named high-risk MSCs, were more common in women with higher risk of ovarian cancer — those of older age or with mutations in the BRCA gene — suggesting that they play a role in cancer initiation.

The findings could also inform approaches for early detection, which are sorely lacking for ovarian cancer. According to Coffman, compounds secreted by high-risk MSCs that are detectable in the bloodstream could act as biomarkers for early-stage ovarian cancer.

For more information about this study, please read the full article.