Ovarian cancer is one of the deadliest cancers affecting women because it is often found only after it has already spread.
Early symptoms can be mild or easy to mistake for other health problems, and there is still no reliable screening test for most women. As a result, many patients are diagnosed at a late stage, making treatment much more difficult.
A new study from Cornell University has uncovered important clues about where the most aggressive form of ovarian cancer begins.
The research, published in Nature Communications, focused on high-grade serous carcinoma (HGSC), the type responsible for most ovarian cancer deaths.
For many years, scientists suspected that this cancer starts in the fallopian tubes rather than in the ovaries themselves.
However, the exact cells responsible remained unclear. The new findings provide the strongest evidence so far that a specific group of cells in the fallopian tubes may be where the disease first develops.
The study was led by Dr. Alexander Nikitin and identified immature cells known as pre-ciliated tubal epithelial cells as the likely starting point for HGSC. These cells are not stem cells, but they have not yet fully developed into mature ciliated cells, which help move eggs and fluid through the fallopian tubes.
The researchers compared how different cell types responded when important cancer-protecting genes were switched off. When the genes were removed from stem cells, the cells simply died. However, when the same genes were turned off in pre-ciliated cells, cancer began to grow, suggesting these cells are much more vulnerable to becoming cancerous.
To test their idea, the team used mice and disabled two tumor suppressor genes called TP53 and RB1. These genes are commonly damaged in people with high-grade serous carcinoma. Only the pre-ciliated cells with these missing genes developed cancer, providing strong evidence that they are the source of the disease.
The scientists also discovered that another gene, called Krt5, is highly active in these pre-ciliated cells. When TP53 and RB1 were switched off in cells with high Krt5 activity, the mice rapidly developed aggressive ovarian cancer. This finding further confirmed the important role of these cells in the disease.
This discovery could lead to major improvements in the fight against ovarian cancer. Doctors may eventually be able to detect the disease much earlier by looking for changes in these cells or by developing tests that measure genes such as Krt5. Researchers may also be able to design new treatments that target the earliest stages of cancer development before tumors become widespread.
Although the experiments were carried out in mice, the fallopian tubes of mice and humans are very similar, giving scientists confidence that the findings may also apply to people.
More studies using human tissue will be needed before new tests or treatments become available, but the research offers fresh hope for earlier diagnosis and more personalized care for women at risk of this deadly cancer.
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