Comprehensive study raises questions about demethylation agents
Agents believed to selectively "restart" genes that limit cancers growth -- a potential treatment option already in early clinical studies -- instead turn off as many genes as they turn on, a team of researchers from the National Cancer Institute and Johns Hopkins has discovered. "We dont know what effect all these changes might have, but its clear that when scientists are looking only at the agents effects on a particular gene or a few particular genes, they arent seeing the whole picture," says Andrew Feinberg, M.D., M.P.H., King Fahd Professor of Medicine at Johns Hopkins. Their report appears in the October issue of Cancer Cell.
The research team probed the global effects of each of three approaches to unhooking methyl groups from genes DNA. Cells normally use methyl groups to "mark" certain genes, indicating whether their instructions should or shouldnt be used for making proteins, but the marks are frequently disrupted in cancer cells. For example, in cancer cells genes that normally stifle cell growth -- so-called tumor suppressor genes -- are shut down because extra methyl groups are hanging on to them. If these extra methyl groups could be removed, the thinking has gone, the gene could be restarted and the cancer slowed or stopped.
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