Gene responsible for dormant ovarian cancer cells elimination
Scientists from the University of Texas have discovered that a single tumor-suppressing gene is of huge importance to understanding (and killing) dormant ovarian cancer cells that persist after initial treatment only to reawaken years later.
A gene called ARHI acts as a switch for autophagy, or self-cannibalization (they eat themselves) in ovarian cancer cells. Often a mechanism for cancer cell death, in this case “self-eating” acts as a survival mechanism for dormant cancer cells.
“Prolonged autophagy is lethal to cancer cells, but a little autophagy can help dormant cancer cells survive, possibly by avoiding starvation,” said one of the researchers Robert Bast, M.D.
“Dormant cells are a major problem in ovarian cancer, breast cancer and other malignancies,” Bast said. “We often see ovarian cancer removed, leaving no remaining sign of disease. After two or three years, the cancer grows back. If any remaining cancer cells had continued to grow normally, the disease should have returned in weeks or months.
“So the assumption is that some cells remain dormant without dividing and without developing a blood supply, but the mechanism for this has not been well understood,” Bast said.
Researchers found that the ARHI is underexpressed in over 70% of ovarian cancers. After they “moved” the level to normal, the “self-eating” process started and the “bad” cells died in a couple of days. Then they tried something different — they moved to human ovarian cancer grafts in mice and found a different effect. ARHI stopped tumor growth and started autophagy, but didn’t kill the cancer cells. When ARHI was turned off at 4 to 6 weeks, the ovarian cancer cells grew rapidly.
“Cancer cells had remained viable during ARHI-induced growth arrest and autophagy, which is consistent with a dormant state,” Bast said. “When we blocked autophagy with chloroquine, a drug also used to treat malaria, regrowth of the cancers was inhibited, suggesting that autophagy had helped the cancer cells to survive in the absence of a blood supply.”
This research is supposed to provide a inducible model for tumor dormancy. Earlier, the lack of of a model like this has hindered understanding of dormant cells and the development of treatments to eliminate them.
The details will be published in the Journal of Clinical Investigation. The research was funded by National Cancer Institute, the National Foundation for Cancer Research and the Blanton-Davis Ovarian Cancer Research Fund.
Source: mdanderson.org
