Researchers have made an important discovery that could change how we find and treat a dangerous type of ovarian cancer.
The study, published in Nature Communications, focused on high-grade serous carcinoma (HGSC), the most aggressive and deadly form of ovarian cancer.
Ovarian cancer is the sixth leading cause of cancer-related deaths in women. Many women with this disease live less than five years after being diagnosed. That’s because it usually doesn’t cause symptoms early on, and there is no good test to catch it before it spreads.
For some time, scientists have believed that this cancer may not start in the ovaries themselves but in the fallopian tubes.
Until now, they weren’t sure exactly where it began. In this new study, led by Dr. Alexander Nikitin from Cornell University, researchers found that a special kind of cell in the fallopian tube, called a pre-ciliated tubal epithelial cell, is likely where this cancer begins.
These pre-ciliated cells are in the middle of changing from stem cells into fully grown ciliated cells, which help move fluids and eggs through the fallopian tubes. In the past, researchers thought that stem cells might be the ones that turn into cancer.
But in this study, scientists found that if cancer-protecting genes were switched off in stem cells, the cells died. If the same genes were switched off in pre-ciliated cells, the cells turned into cancer.
The team tested this using specially bred mice. They looked at two tumor suppressor genes—TP53 and RB1 (called Trp53 and Rb1 in mice)—which are often damaged in people with HGSC. When these genes were turned off in pre-ciliated cells, the mice developed cancer, but when turned off in other cells, cancer didn’t grow.
This is a big step forward because now scientists know exactly which cell may cause this aggressive cancer. Even better, they understand the process these cells go through, called ciliogenesis, or the way they grow tiny hair-like structures called cilia.
Since scientists already know a lot about ciliogenesis, it may be easier to develop ways to stop the cancer from forming.
They also found that a gene called Krt5 is very active in these pre-ciliated cells. When they turned off Trp53 and Rb1 in cells with high Krt5, the mice quickly developed cancer. This helps confirm that these cells are the source of HGSC.
This finding could lead to big improvements: Doctors might be able to detect ovarian cancer earlier by spotting pre-ciliated cells before they become cancer. Treatments could focus on stopping ciliogenesis to prevent cancer from forming. Genes like Krt5 might be used in new screening tests to find early warning signs.
Although this research was done in mice, the scientists say human fallopian tubes are very similar, so these results will likely apply to people too. More studies are needed to confirm this in human tissue, but the discovery gives real hope for earlier diagnosis and better treatment options for ovarian cancer.
Dr. Nikitin and his team believe this breakthrough could help create personalized treatments for women at high risk and could improve both survival rates and quality of life.
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