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Tissues known as organoids have the potential to predict which individuals will develop ovarian cancer years or even decades in advance, allowing for early detection and prevention strategies.
Stem cell scientists have revealed the origins of a common ovarian cancer by modeling fallopian tube tissues, which has allowed them to characterize how a genetic mutation puts women at high risk of suffering from this cancer and predict many years in advance whether they will suffer from it, as published in the journal 'Cell Reports'.
Specifically, the tissues created, known as organoids, have the potential to predict which individuals will develop ovarian cancer years or even decades in advance, which would allow early detection and prevention strategies.
Ovarian cancer is the leading cause of death from gynecological cancer, in part because the symptoms are usually subtle and most tumors elude detection until they are in advanced stages and have spread beyond the ovaries.
While the lifetime risk of developing ovarian cancer is less than 2% for the general female population, The estimated risk for women carrying a mutation in the so-called BRCA-1 gene is between 35% and 70%., according to the American Cancer Society.
Given these very high probabilities, some women with mutations in the BRCA-1 gene opt for surgical removal of the breasts or ovaries and fallopian tubes, although they never develop cancers in these tissues.
The results of the new study could help doctors determine which of These women are more likely to develop ovarian cancer in the future and which are not and look for new ways to block the process or treat the cancer.
"We created these fallopian organoids using cells from women with mutations in the BRCA-1 gene who had ovarian cancer," explains Dr. Clive Svendsen, executive director of the Cedars-Sinai Board of Governors Institute for Regenerative Medicine, in USA.
"Our data support recent research indicating that ovarian cancer in these patients actually begins with cancerous lesions in the lining of the fallopian tubes," he continues. "If we can detect these abnormalities early, we may be able to short-circuit ovarian cancer."
Svendsen, professor of Biomedical Sciences and Medicine, is a co-author of the new study, conducted at Cedars-Sinai. The other corresponding author is Dr. Beth Karlan, now professor of Obstetrics and Gynecology at the UCLA David Geffen School of Medicine and director of cancer population genetics at the UCLA Jonsson Comprehensive Cancer Center.
To make their discoveries, the research team generated induced pluripotent stem cells (IPSCs), which can produce any type of cell. They started with Blood samples taken from two groups of women: young ovarian cancer patients who had the BRCA-1 mutation and a control group of healthy women. The researchers then used the iPSCs to produce organoids that modeled the lining of the fallopian tubes and compared the organoids from the two groups.
"We were surprised to find multiple cellular pathologies consistent with cancer development only in the organoids of patients with BRCA-1. -recalls Nur Yucer, project scientist in Svendsen's laboratory and first author-. "Organoids derived from women with the most aggressive ovarian cancer showed the most severe organoid pathology."
In addition to showing how ovarian cancer is "seeded" in the fallopian tubes of women with mutated BRCA-1, organoid technology can potentially be used to determine if a drug could work against disease in an individual, adds Svendsen.
Each organoid carries the genes of the person who provided the blood sample, making it a "twin" of that person's fallopian tube lining. Multiple drugs can be tested on organoids without exposing the patient to them.
"This study represents an exciting use of IPSCs, which "We get closer than ever to significantly improving outcomes for women with this common type of ovarian cancer.", highlights Jeffrey Golden, vice dean of Research and Graduate Education and director of the Burns and Allen Research Institute at Cedars-Sinai.
"Building on these findings may one day allow us to offer life-saving early detection of ovarian cancer to women carrying the BRCA-1 mutation and create effective, individualized prevention and, if necessary, treatment strategies," he says. .
