Epithelial ovarian cancer accounts for approximately 90% of all ovarian cancers. Most epithelial ovarian cancers, especially the high-grade serous subtype, tend to develop resistance to platinum-based chemotherapy drugs.
The researchers identified the microRNA miR-506 as a likely robust clinical marker for epithelial ovarian cancer patient survival and chemotherapy response and as a potential therapeutic agent owing to its ability to sensitize cancer cells to chemotherapy.
“We had previously found that miR-506 is a potent inhibitor of a process known as epithelial-to-mesenchymal transition, which is associated with chemotherapy resistance,” said Wei Zhang, Ph.D., a professor in the Department of Pathology and senior author of the study’s report.
Using data from The Cancer Genome Atlas and three independent data sets, Dr. Zhang and his colleagues found that high levels of miR-506 expression were associated with longer progression-free and overall survival in patients with epithelial ovarian cancer.
The researchers then performed in vitro and in vivo experiments to elucidate the role of miR-506 in chemotherapy response. In human high-grade serous epithelial ovarian cancer cells, miR-506 directly targeted the double-strand DNA damage repair gene RAD51, sensitizing the cells to damage from platinum-based chemotherapy drugs. In a mouse model of high-grade serous epithelial ovarian cancer, the addition of miR-506–loaded nanoliposomes to platinum-based chemotherapy significantly improved treatment responses.
“This study provides further insight into the role of miR-506 in augmenting chemotherapy responses by directly affecting the DNA repair process used by cancer cells to counter DNA damage caused by chemotherapy,” Dr. Zhang said.
The results of the study were published in the July issue of the Journal of the National Cancer Institute.
OncoLog, September 2015, Volume 60, Issue 9