Recent results from Icahn School of Medicine at Mount Sinai researchers have shown that two approved cancer drugs have the capacity to turn on a gene responsible for cancer cells’ dormancy.
In the study entitled, “NR2F1 controls tumor cell dormancy via SOX9- and RARβ-driven quiescence programmes,” published in Nature Communications, the research team found that the NR2F1 gene works as a regulator of cancer cell dormancy or proliferation, depending on whether it is turned on or off.
Through the combination of azacytidine and retinoic acid, the team observed that there was a significantly increased level of active NR2F1 in tumor cells, both in animal models of prostate cancer and in actual prostate cancer cells from human patients.
The data obtained from this study suggests that NR2F1 acts as a master regulator of cancer cell growth, and can influence different genes that dictate if cancer cells remain inactive or proliferate intensely, eventually leading to cancer spreading throughout the body (metastasis).
Furthermore, the authors found that during human development, NR2F1 controls genetic programs in the embryo’s stem cells, where it can direct neuronal development.
“Our results explain why some tumor cells scattered through the body are committed to remaining harmless for years, while others cause active disease,” Julio A. Aguirre-Ghiso, PhD, Professor of Medicine, Hematology and Medical Oncology, and Otolaryngology at the Icahn School of Medicine, said in a news release. “In finding this master switch we found a way to analyze tumor cells before treatment to determine the risk of a cancer recurrence or metastasis.”
“Azacytidine and retinoic acid, the latter a form of vitamin A, prevented tumor cells from rapidly multiplying, restored normal cell function, and activated several tumor suppressor genes that are often turned off in tumors,” added study co-leader Maria Soledad Sosa, PhD, a postdoctoral fellow in Hematology at the Icahn School of Medicine. “We now have strong evidence that combining these well-known drugs may have a profound, long-lasting therapeutic effect.”
This current investigation is based on the team’s previous findings, which indicated that decreasing the levels of TGFβ2 and p38, two tumor suppressor genes, could re-activate dormant tumor cells and induce tumor growth and metastasis. However, upon addition of azacytidine and retinoic acid, TGFβ2 expression and p38 activation were recovered, allowing tumor cells to remain dormant.