Johns Hopkins scientists have identified what they are calling a "master regulator" gene that halts the growth and spread of cancer and may be the key to developing a new treatment for tumors that are resistant to current drugs.
The gene, when repressed in cancer cells, puts a halt to their growth and a range of processes required for tumors to enlarge and spread to distant sites — a life-threatening process known as metastasis. The research, published in the Public Library of Science journal PLOS ONE, found that blocking the action of that single gene renders tumors less aggressive.
"This master regulator is normally turned off in adult cells, but it is very active during embryonic development and in all highly aggressive tumors studied to date," said researcher Linda Resar, M.D., an associate professor of medicine, oncology, and pediatrics, and affiliate in the Institute for Cell Engineering at the Johns Hopkins University School of Medicine.
"Our work shows for the first time that switching this gene off in aggressive cancer cells dramatically changes their appearance and behavior."
Dr. Resar has been investigating genes related to cancer and stem-cell growth for two decades.
"Many investigators consider cancer cells to be the evil twin of stem cells, because like stem cells, cancer cells must acquire special properties to enable the tumor to grow and metastasize or spread to different sites," she explained.
In a past study, she and her team devised techniques to block the so-called HMGA1 gene in stem cells and found it is essential for turning adult cells into stem cells.
For the new study, Dr. Resar’s team applied the same techniques to several strains of human breast cancer cells in the laboratory and in mice. When the researchers blocked the action of the HMGA1 gene, they found the tumors grew very slowly and did not spread.
"From previous work, we know that HMGA1 turns on many different genes needed during very early development, but it's normally turned off by the time we're born," said Sandeep Shah, who led the study. "Flipping that master regulator back on seems to be necessary for a cancer to become highly aggressive, and now we've seen that flipping HMGA1 off again can reverse that aggressive behavior."
The next step, Dr. Resar said, is to try to develop a therapy based on the research, which was partly funded by the National Cancer Institute.
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