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Joyce F. Liu, MD, MPH
Joyce F. Liu, MD, MPH
Posted: Friday, February 21, 2025
Although the involvement of the androgen receptor pathway in ovarian cancer development has been increasingly studied, Setsuko K. Chambers, MD, of the University of Arizona Cancer Center, Tucson, and colleagues suggest that the impact of antiandrogen agents that may prevent ovarian cancer remains unknown. These investigators assessed how the antiandrogen agent flutamide appears to alter microRNA (miRNA) expression in women who are at high risk for ovarian cancer, and they published their findings in Scientific Reports.
“This is particularly promising for high-risk women with decreased miRNA-449 expression, who may represent the subgroup most likely to benefit,” the study authors concluded. “Moving forward, further studies are needed to ascertain whether the flutamide-induced miRNA-449 restoration effectively translates into a reduced risk of developing ovarian cancer in these patients.”
The study authors collected tubal and ovarian tissues that did not have tubal cancer, ovarian cancer, peritoneal cancer, or serous tubal intraepithelial carcinoma from high- and low-risk patients. High-risk women were either untreated or flutamide-treated, and low-risk women represented the control group. Each sample cohort underwent miRNA sequencing to detect miRNA levels in their respective tissues.
Flutamide was observed to normalize miRNA levels in high-risk tissues as well as to upregulate the miRNA-466 family of gene-expression RNAs to levels seen in low-risk tissues. Subsequent analyses conducted on ovarian cancer cell lines SKOV3 and Hey, in addition to primary ovarian epithelial cells, demonstrated that flutamide increased not only miRNA-449a levels but also miRNA-449b-5p levels.
Of note, miRNA-449a and miRNA-449b-5p—but not miRNA-449c-5p—were observed to target colony-stimulating factor 1 receptor (CSF1R) and other androgen receptor mRNAs. Of note, mimics of these miRNAs that were introduced to these tissues also reduced protein and mRNA levels of CSF1R and androgen receptors, suggesting they play a crucial role in ovarian cancer initiation; introducing these miRNA mimics also appeared to inhibit ovarian cancer cell migration.
DIsclosure: The study authors reported no conflicts of interest.
