Researchers have discovered the likely origin of a deadly form of ovarian cancer, offering new hope for early detection and better treatments.
The study, published in Nature Communications, identifies a specific type of cell in the fallopian tube that is particularly prone to developing high-grade serous carcinoma (HGSC), the most aggressive form of ovarian cancer.
Ovarian cancer is the sixth leading cause of cancer-related deaths in women, with most patients surviving less than five years after diagnosis.
This is partly because there are no symptoms in the early stages and no reliable tests for early detection.
Scientists have long suspected that HGSC begins in the fallopian tubes rather than the ovaries, but the exact origin remained unclear—until now.
The research team, led by Dr. Alexander Nikitin from the College of Veterinary Medicine at Cornell University, found that a specific group of cells in the fallopian tube, known as pre-ciliated tubal epithelial cells, are highly susceptible to developing cancer.
These cells act as intermediaries between stem cells and fully developed ciliated cells, which help move fluids and eggs through the fallopian tubes.
While previous studies focused on stem cells as a potential source of cancer, this study found that stem cells themselves do not turn cancerous when key tumor-suppressing genes are turned off. Instead, the pre-ciliated cells—those in transition from stem cells to fully formed ciliated cells—are the ones at risk.
To better understand how cancer forms, the researchers studied genetically engineered mice.
In human HGSC cases, mutations in two genes—TP53 and RB1—occur in the vast majority of cases. These genes help prevent cells from turning cancerous, so when they are inactivated, cells are more likely to become cancerous.
In the study, the scientists silenced Trp53 (the mouse equivalent of TP53) and Rb1 in different types of cells in the fallopian tube. They found that:
- When stem cells lost these tumor-suppressing genes, they simply died instead of turning into cancer cells.
- When pre-ciliated transitional cells lost these genes, they became cancerous, leading to the development of HGSC.
This finding reveals that pre-ciliated cells are the key culprits in the fallopian tube where this aggressive cancer originates.
Potential for Early Diagnosis and New Treatments
One of the most promising aspects of this discovery is that the process of ciliogenesis (the formation of cilia) is already well understood by scientists. Since pre-ciliated cells are in an intermediate stage of development, researchers now have a better idea of what to look for when designing diagnostic tools.
One specific gene, Krt5, was found to be highly active in these pre-ciliated cells. In further experiments, when the researchers silenced Trp53 and Rb1 in Krt5-positive cells, the mice quickly developed high-grade serous carcinomas, confirming their role in cancer formation.
This discovery opens up multiple possibilities:
- Early Detection – If pre-ciliated cells can be identified in their transitional state, doctors may be able to detect ovarian cancer before it fully develops, increasing the chances of early treatment.
- New Therapies – By targeting the molecular pathways that regulate ciliogenesis, researchers may be able to develop drugs that prevent pre-ciliated cells from turning cancerous.
- Better Screening Methods – Identifying markers like Krt5 could help scientists create tests to detect at-risk cells before they become tumors.
While the study was conducted in mice, the similarities between mouse and human fallopian tube structures suggest that these findings could apply to human ovarian cancer as well.
Further research is needed to confirm these results in human tissue samples, but this discovery brings new hope for improved diagnosis and treatment of a cancer that has long been difficult to detect in its early stages.
Dr. Nikitin and his team believe this breakthrough could lead to personalized treatments for women at risk of ovarian cancer and, ultimately, a better chance of survival.
If you care about cancer risk, please read studies that exercise may stop cancer in its tracks, and vitamin D can cut cancer death risk.
For more information about cancer, please see recent studies that yogurt and high-fiber diet may cut lung cancer risk, and results showing that new cancer treatment may reawaken the immune system.
The research findings can be found in Nature Communications.
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