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It turns out that epigenetic therapy supposed to fight against lung cancer has opposite effects.
Researchers at the Boston Children's Hospital have indicated that this therapy stimulates cancer stem cells that are thought to drive tumors. They reported a strategy that reduces these cells, reducing lung cancer in mice. The findings of the study are published in Nature Communications Journal.
Epigenetic therapy is the way to target enzymes that alter the functioning of genes. It has a growing interest in the field of cancer.
Cancer stem cells have been identified in blood cancers and various solid tumors. They are a tiny fraction of tumor cells but can regenerate cancer by themselves.
Previous studies have shown that cancer stem cells play a role in adenocarcinoma, the most common type of lung cancer. When they transplanted cancer stem cells from a diseased mouse, previously healthy mice developed lung cancer.
The new study examined an epigenetic therapy that inhibits the enzyme G9a, a type of histone methyltransferase. G9a was thought to promote cancer and some studies have suggested that G9a inhibition was an effective strategy in some cancers, including adenocarcinoma.
"People had been examining cell lines from lung tumors and had discovered that they were sensitive to G9a-inhibiting drugs," said Rowbotham, the study's first author. "In general, tumor cell populations, these drugs would slow growth or even kill cells, but we found that these drugs also made surviving tumor cells more related to the stem." We predicted that this would advance the disease, and we saw. "
The team first looked at the adenocarcinoma cell lines and discovered that when the cells were treated with G9a, they looked more like stem cells. They then transplanted cancer stem cells into live mice and followed the evolution of adenocarcinoma. When they destroyed the G9a gene in lung tumors, the tumors grew larger and spread further.
Previous studies could not see that cancer stem cells were still there, and there are more when you deal with these drugs. Since they represent only a small fraction of the tumor, anything that affects them can easily be omitted.
The researchers also discovered potentially better enzymes to target: histone demethylases. Their action is chemically opposite to that of G9a, eliminating a methyl group of histone, where G9a adds one. When Rowbotham neutralized the demethylase enzyme gene and added the drug that prevents it from functioning, he was able to make the cells look less like cancer stem cells in a box and behave less like cancer stem cells in live mice. When he administered demethylase inhibitors to mice with established lung tumors, the progression of the cancer was slowed down and the animals survived longer than the untreated mice.
(This story has not been changed by Business Standard staff and is generated automatically from a syndicated feed.)
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