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Thanks, Epigenetics!

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Researchers at Johns Hopkins University have created a novel combination cancer therapy that is proving effective in some non-small-cell lung cancer patients, reports Shari Roan at the Los Angeles Times' Booster Shots blog. The two-drug therapy — a combination of azacitidine and entinostat — "represents a new treatment approach called epigenetic therapy and signals another potential avenue to eradicate tumors," Roan says. In the study, recently published in Cancer Discovery, the researchers administered the combination therapy to 45 patients with advanced, metastatic disease, who had failed to respond to previous treatment. "The average group survival rate was 6.4 months compared with the average survival rate of about four months for patients receiving standard treatment," Roan says. "Among the patients who had two or more treatments, survival averaged about eight months. Moreover, a few patients had dramatic responses. Seven people are still alive, with one person marking four years of survival."

There are still some questions about how exactly the drugs affect cancer cells, Roan adds. Azacitidine is thought to block DNA methylation instead of directly killing cancer cells. The researchers say their new treatment approach aims to affect gene expression without killing cancer cells, in order to allow those diseased cells to reprogram themselves. "To their surprise, researchers also found that some of patients who went on to have traditional chemotherapy after the epigenetic therapy responded much better than would have been expected for such advanced disease," Roan says. The thinking is that perhaps the epigenetic therapy paves the way for chemotherapy to kill the cancer.

The researchers are now looking to see which patients responded better than others, and why. They are analyzing possible predictive biomarkers — a test for these markers could theoretically be developed to determine which patients will respond to this kind of treatment, Roan says. And other trials are also underway to test epigenetic therapies in other cancers.

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