Major discovery identifies the cause of ovarian cancer

Ovarian cancer is the deadliest form of gynecologic cancer, taking the lives of more than 13,000 women in the U.S. each year. The most common type, high-grade serous ovarian carcinoma (HGSOC), is particularly dangerous because it is often diagnosed at a late stage when it has already spread.

Early detection methods are lacking, and symptoms are vague, making prevention and timely treatment a challenge. Researchers are working to uncover the mechanisms behind HGSOC to develop new strategies for early diagnosis and prevention.

For many years, scientists believed that ovarian cancer began in the ovaries. However, recent evidence shows that most HGSOC cases originate in the fallopian tube epithelium. The earliest stage of this cancer, called a serous tubal intraepithelial carcinoma (STIC), consists of mutated cells that show abnormal growth patterns.

STIC lesions share similarities with precancerous colon polyps, which can develop into colorectal cancer. However, while colon polyps can be removed to prevent cancer, there is no equivalent strategy for ovarian cancer because its early warning signs are harder to detect.

Most research has focused on the mutated epithelial cells that form STIC lesions, but scientists at the University of Pittsburgh took a different approach. They examined the surrounding stromal tissue—the supportive connective tissue that interacts with epithelial cells.

Their study, published in Cancer Discovery, found that certain progenitor cells in the stroma, called mesenchymal stem cells (MSCs), play a major role in cancer development.

MSCs normally help repair and maintain healthy tissues, but in the presence of cancer, they undergo changes that make them support tumor growth.

The researchers discovered that even in women without cancer, some MSCs already resemble the cancer-associated MSCs seen in ovarian tumors. These high-risk MSCs (hrMSCs) were more common in women who carried BRCA1 or BRCA2 gene mutations or were older, two groups known to have a higher risk of developing ovarian cancer.

To investigate the impact of hrMSCs, the researchers introduced them into organoids—lab-grown mini-organs derived from patient fallopian tube tissue.

The results were alarming: the presence of hrMSCs transformed normal epithelial cells into cancerous ones. The hrMSCs also encouraged tumor growth and made cells more resistant to chemotherapy, showing that they play an active role in cancer progression.

These findings suggest that hrMSCs create a microenvironment that fosters cancer initiation. They increase DNA damage in epithelial cells and promote cell survival after genetic mutations occur.

The loss of a protective antioxidant, AMP kinase, in hrMSCs was linked to increased levels of a protein called Wilms Tumor Protein 1 (WT1), which triggers molecular changes that damage DNA and drive cancer formation.

The discovery of hrMSCs as a trigger for ovarian cancer opens new doors for prevention. Since drugs that restore AMP kinase levels already exist, they could be tested for their ability to stop or reverse the early cellular changes that lead to ovarian cancer.

Another promising avenue is early detection. The researchers found that hrMSCs secrete compounds into the bloodstream, which could serve as biomarkers for detecting ovarian cancer in its earliest stages. Identifying women with these markers could allow doctors to monitor high-risk individuals and intervene before the disease develops.

Co-senior author Dr. Lan Coffman, an oncologist at the University of Pittsburgh, emphasized the importance of these findings. "Understanding the underlying biology of how ovarian cancer forms is critical to improving outcomes for our patients," she said. "This is the first report that stromal changes in the fallopian tube actually have a causative role in ovarian cancer initiation. It also points to a path where we might be able to intervene."

With ovarian cancer remaining a major cause of cancer-related deaths, these insights bring hope for more effective prevention and early detection strategies. By targeting the tumor-supportive stroma and understanding its role in cancer formation, researchers are paving the way for life-saving advancements in ovarian cancer treatment.

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.

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