Imma Perfetto
Cosmos science journalist
In vital progress in the fight against high-grade serious carcinoma, one of the most aggressive and common forms of ovarian cancer, researchers have identified a subset of cells in the fallopian tubes that drive the disease.
The findings, presented in a new study in the journal Cancer Discovery, provide a new target for developing ways to prevent or detect the early stages of the disease.
“Ovarian cancer is the leading cause of death from gynaecologic cancer in the Western world,” says Lan Coffman, co-senior author of the study and associate professor of malignant haematology and medical oncology at the University of Pittsburgh in the US.
“But we currently have no way to detect it early and no prevention strategies apart from surgical castration, which is only indicated in high-risk women.
“Understanding the underlying biology of how ovarian cancer forms is critical to improving outcomes for our patients.”
High-grade serous carcinoma (HGSC) begins in the fallopian tubes. The epithelial cells which line it transform into precursor lesions known as serious tubal intraepithelial carcinoma (STIC), which then further develop into tumours.
To understand how this happens, Coffman and her team looked to the stroma – the non-cancerous connective tissue in the fallopian tubes.
They wanted to know when mesenchymal stem cells (MSCs), which are normally involved in the growth and repair of healthy tissue, become reprogrammed by tumour cells to support cancer growth.
However, the team was surprised to find cells that looked like cancer-associated MSCs already in the fallopian tubes of patients who did not have ovarian cancer. These high-risk MSCs were more common in women with higher risk of ovarian cancer – those of older age or with mutations in the BRCA gene.
When the researchers introduced these high-risk MSCs into organoids grown from fallopian tube tissue, the previously healthy epithelial cells became cancerous.
“High-risk MSCs promote DNA damage in epithelial cells and then help those mutated cells survive,” explains Coffman.
“It’s the perfect storm for cancer initiation.”
They found that high-risk MSCs did this because they lost an antioxidant enzyme, which drove the formation of compounds that cause DNA damage.
“This is the first report that stromal changes in the fallopian tube actually have a causative role in ovarian cancer initiation,” says Coffman.
“It also points to a path where we might be able to intervene.”
For example, existing drugs could potentially prevent or reverse early changes in the stroma that lead to ovarian cancer. And, according to Coffman, compounds secreted by high-risk MSCs that are detectable in the bloodstream could act as biomarkers for detecting early-stage ovarian cancer.
