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Combination epigenetic therapy clinical trial results
Date:11/10/2011

A new type of therapy aimed at reversing the gene-silencing that promotes cancer-cell growth has shown promising results in a small clinical trial conducted by researchers at the Johns Hopkins Kimmel Cancer Center. Forty-five late-stage lung cancer patients who received a two-drug combination designed to restore anti-cancer gene activity survived about two months longer than the expected four months, and two patients showed complete or near-complete responses despite having progressive disease after multiple standard therapies.

In the study, reported in Cancer Discovery on Nov. 9, 2011, the Hopkins researchers treated non-small-cell lung cancer patients with a combination of the drugs azacitidine and entinostat. Azacitidine removes methyl groups from genes; entinostat inhibits histone deacetylation, a closely related process that also contributes to gene-silencing.

"We hope these results lead to a larger, more definitive clinical trial of this drug combination," says Charles Rudin, M.D., Ph.D., professor of oncology and director of the Upper Aerodigestive Cancer Program at Hopkins' Kimmel Cancer Center. Rudin led the team of physicians and cancer biologists who conducted the study.

It is believed to be one of the first to show promising results for "epigenetic" anti-cancer therapies in solid tumors. Johns Hopkins researchers previously tested the drug combination in leukemia patients. Laboratory results suggest that epigenetic treatments aim not to kill cancer cells directly but instead may reprogram their patterns of gene expression so that they lose their capacity for uncontrolled growth. A normal cell has a specific pattern of gene expression, in which some genes are active and others are suppressed, and a derangement of this pattern frequently contributes to cancer, in part by silencing genes whose activity would normally stop a cell from becoming cancerous. Cancer cells also have permanent genetic mutations, which cann
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Contact: Vanessa Wasta
wasta@jhmi.edu
410-614-2916
Johns Hopkins Medical Institutions
Source:Eurekalert

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