A new approach for the treatment of lung cancer, which aims to activate dormant blocking tumor genes has shown promising results in a small clinical trial. The 45 patients on average lived a few months longer than they would have without treatment, and tumors of two patients almost completely disappeared. The results suggest that the so-called epigenetic drugs worth exploring further, say the authors.
Most drugs against cancer attempt to kill tumor cells. "Epigenetic" drugs are supposed to work differently, resetting the genetic activity of a tumor cell so that it divides rather than simply eliminate the cell. Epigentics the term refers to chemical modifications of DNA that control gene activity, turning their expression on or off, for example; into a kind of epigenetic conscripts methyl chemicals can attach to DNA and block of being transcribed into a protein. In many types of cancer, for example methylation silenced suppressor genes tumor.
cancer biologists such as Stephen Baylin of Johns Hopkins University in Baltimore, Maryland, suggested that drugs that strip the methyl groups from DNA could prevent cancer cells from growing by changing these tumor suppressor genes back. In fact, a drug called azacytidine demethylates that DNA has been approved since 04 to treat a type of blood cancer. However, tests in the 1970s and found that 80 azacytidine was too toxic for patients with solid tumors.
But Baylin and other Hopkins researchers recently decided to see if azacytidine could help patients with solid cancers when given in low doses strong enough to reset the DNA methylation patterns, but not kill cells. Led by Charles Rudin oncologist, the team identified 45 patients with lung cancer at an advanced stage where other therapies had failed and were given low doses of azacytidine and another epigenetic drug that opens the package protein around the DNA.
The study was a modest success. The average patient lived 6.4 months - only 2 months longer than they would have without treatment. However, tumors of two or almost completely disappeared patients. Although their cancer returned later, one of these patients is still alive after 2.5 years. And four patients who do not do well on epigenetic therapy responded strongly to cancer drugs subsequent standard; Both lived 4 years, well beyond what was expected in view of their cancer.
Why some patients are much more successful than others? The Hopkins group speculates the reason is that tumors only a few patients were driven by epigenetics. They tested the tumor DNA from 26 of 45 patients for four genes which when methylated, predict a tumor of the lung will soon grow back after surgery. Patients whose tumors had at least two methylated genes before treatment, then lost methyl groups lived on average 10 months, four months longer than patients without that pattern, according to the study, published today in cancer Discovery .
"there is not a home run, but there is a real input in this area," says Baylin. The results suggest that doctors could test the models of patient gene methylation to know if their tumors can be treated with epigenetic drugs, he said. His team is also intrigued by the suggestion that epigenetic drugs can first tumor cells to better respond to other drugs, a possibility that they hope will be tested in another trial.
Two researchers not involved in the study described as "revolutionary" during a press conference today. "I think this finding is incredibly exciting and will trigger whirlwind of activity, research in the lung cancer community, "said Jeffrey Engelman oncologist at Massachusetts General Hospital in Boston.
Others are cautious. Molecular biologist Frank Lyko the German Research on Cancer in Heidelberg agrees that the study "strongly suggest" that the combo of epigenetic drugs work on lung cancer. But he said more accurate measurements of patient tumor methylation patterns are needed to definitively show that the drugs worked through epigenetic effects, not another mechanism. The analytical results reported in the paper, he said, are not "convincing".
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