Spotted! New Therapeutic Targets for Ovarian Cancer
(Ivanhoe Newswire) — From harmless to deadly – normal cells surrounding ovarian cancer cells can be changed to promote tumor growth. Now, a new understanding of what causes this switch may provide researchers with therapeutic targets to battle the deadly disease.
"New approaches for treating patients with ovarian cancer are desperately needed," said Ernst Lengyel, M.D., Ph.D., professor in the department of obstetrics and gynecology at the University of Chicago.
"There have been no new approaches introduced into the clinic for quite some time, and we have seen no major improvements in patient survival over the years."
So Lengyel and his colleagues set out to learn how normal stromal cells are transformed into cancer-associated fibroblasts, which are found in the tissue immediately surrounding the ovarian cancer cells.
"The strength of our study lies in the fact that we used cells from patients, rather than cell lines," Lengyel said. "This means that our model system reflects as closely as possible the clinical situation in patients."
The data indicated that cancer-associated fibroblasts from patients with ovarian cancer had abnormal patterns of expression of small molecules called microRNAs compared with normal and tumor-adjacent fibroblasts.
MicroRNAs are regulators of gene expression and help direct cell function, meaning modified patterns of microRNA expression change cell function.
Lengyel and colleagues further studied the microRNA most upregulated, or increased in quantity, in cancer-associated fibroblasts, and the two microRNAs most significantly downregulated. They then changed the pattern of expression of these three microRNAs to mimic the pattern they had seen in cancer-associated fibroblasts. They found that the normal fibroblasts were converted into cells with characteristics of those associated with cancer. In addition, the cells had reprogrammed by altering microRNA expression and enhanced the growth of tumor cells in a mouse model of ovarian cancer.
Restoring the pattern of expression of the three microRNAs to normal in cancer-associated fibroblasts reduced their cancer-promoting characteristics.
"Our work suggests that it might be possible to modify microRNA expression in cancer-associated fibroblasts for therapeutic benefit," Lengyel said. "Therapeutic approaches targeting microRNAs in cancer cells are under development."
Treatments targeting microRNAs in cancer-associated fibroblasts may be particularly effective because the cells are genetically stable. Cancer cells are not. Therefore, the risk that cancers will become unresponsive to the treatments is less likely than it is for treatments targeting cancer cells, Lengyel said.
Source: Cancer Discovery, a journal of the American Association for Cancer Research