A major scientific breakthrough has revealed the origin of one of the most aggressive forms of ovarian cancer—high-grade serous carcinoma.
This type of cancer, which is the sixth-leading cause of cancer death in women, has now been traced to a specific type of cell in the fallopian tube.
High-grade serous carcinoma is especially deadly because it usually has no clear symptoms and no reliable early detection tools. By the time most women are diagnosed, it is already too late for effective treatment, and many patients do not survive beyond five years.
The new study, published in Nature Communications, identified pre-ciliated tubal epithelial cells as the likely starting point of the disease.
These are transitional cells in the fallopian tube, sitting between stem cells and fully developed ciliated cells that help move fluids and eggs. Researchers found that these pre-ciliated cells are particularly prone to becoming cancerous.
Dr. Alexander Nikitin, a professor at Cornell University’s College of Veterinary Medicine and the senior author of the study, said: “We not only identified the cells where the cancer originates, but we also uncovered mechanisms that could lead to new diagnostic tools and therapies.”
The research was done in mice, where the fallopian tube is known as the uterine tube. Nikitin’s earlier studies had linked the origins of this cancer to the ovaries, but this is the first time specific cancer-prone cells in the fallopian tube have been identified.
Scientists mapped out all the different cell types in the uterine tube and examined how genetic mutations could turn them cancerous.
In human cases of high-grade serous carcinoma, mutations in two genes—TP53 and RB1—are very common. TP53 is mutated in over 96% of cases, and parts of the RB1 pathway are altered in over 60% of cases. Both genes normally act as tumor suppressors.
Surprisingly, when the researchers inactivated TP53 and RB1 in stem cells of the fallopian tube, no cancer developed even after a year; instead, the stem cells died. But when the same mutations were introduced into pre-ciliated cells, high-grade serous carcinoma developed quickly in the mice.
Using single-cell sequencing, the researchers identified pre-ciliated cells that expressed a gene called Pax8, which is often linked to this cancer type. These Pax8-positive cells, along with another marker gene called Krt5, were particularly vulnerable to becoming cancerous when TP53 and RB1 were disabled.
The process these cells are undergoing—ciliogenesis, or the formation of hair-like cilia—is already well understood in biology. This existing knowledge could make it easier for scientists to develop new ways to detect the cancer early or to target it with treatments.
By pinpointing the exact cell type and genetic pathways that give rise to high-grade serous carcinoma, researchers now have a clearer path toward earlier detection and better therapies. This discovery offers new hope for improving survival rates for a disease that has long been difficult to diagnose and treat.
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