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Drugs That Control Genes May Treat Lung Cancer

Researchers Report Some Success Against Advanced Lung Cancer With Epigenetic Drugs

New Approach to Treating Cancer continued...

Two patients in the study had remarkable results.

In one patient, the cancer completely disappeared for 14 months, though she later developed a different kind of lung cancer that proved fatal.

 A second patient saw tumors that had spread to his liver vanish and the primary tumor in his lung shrink.

Researchers described the drugs as well tolerated with few side effects for patients. The most commonly reported side effect was fatigue.

Despite their promising results, researchers say there's still a lot more to be learned before the epigenetic therapy becomes a mainstream treatment.

"This trial is small," Rudin says, "and these results certainly need to be confirmed in a larger study population."

Researchers say larger studies testing the drug combo are already underway.

"This is not yet a study that would in any way impact standard of care for this disease. But I think it opens up a new avenue that may be of real benefit to these patients," Rudin says.

Understanding Epigenetics

The drugs are believed to work by blocking a process that stops the activity of genes that naturally block tumor growth. In some cancers, these genes are switched off, taking out one of the body's natural defenses.

In contrast to drugs that target a specific gene or a mutation in a gene when it shows up in cancers, epigenetic therapies aim to control gene expression.

To help explain how it works, researcher Stephen A. Baylin, MD, professor and deputy director of the Kimmel Cancer Center at Johns Hopkins University, likens genes to the hard drive on a computer.

"But the hard drive needs a software package to tell it how to function and epigenetics is essentially that software package," Baylin says. Baylin says he has no financial interest in the drugs tested in the study, but that he has helped develop a blood test used in the research.

"In every patient's cancer, of every type, hundreds of genes can also be affected by abnormalities in the software package, or epigenetic abnormalities, and that's what we are theoretically trying to target," he says.

Who Will Benefit?

One key question is why some people in the study had dramatic responses to the medications when others did not.

To answer that, researchers gave 26 patients in the study blood tests to check the function of four genes that were shown in an earlier study to affect how aggressively lung cancers might spread.

If at least two of the four genes were switched off, lung cancers are more likely to recur and spread.

And indeed, in 10 patients who had at least two silenced genes, using the epigenetic drug therapy to turn those genes back on increased survival significantly compared to 16 patients whose genes weren't switched off in the first place.

"The investigators have done a great job in trying to identify specific biomarkers," Engleman says. "We need to know which patients will respond to these therapies."


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