A gene that has been methylated has been changed ever so slightly. Like a gun with the bullets taken out, it looks much the same — except what was once a powerful weapon is now about as deadly as a doorstop.

Hopkins scientists are hot on the trail of understanding DNA methylation, and how to reverse it in prostate cancer. One of them is urologist Mark L. Gonzalgo, M.D., Ph.D., the Nancy and Jim O'Neal Scholar.

Like a gun with the bullets taken
out, the altered gene looks much
the same—except what was once
a powerful weapon is now about
as deadly as a doorstop.

"Methylation is a natural phenomenon," he explains, and most of the time, it serves a useful purpose. For example, "we would not want our prostate to make hemoglobin, the protein required to carry oxygen in our blood cells. But sometimes important genes can become methylated, leading to the development of cancer." Using a mouse model, Gonzalgo is studying drugs called "demethylating agents" — by themselves and in combination with drugs that inhibit tumor growth, called histone deacetylase (HDAC) inhibitors — looking for the right formula to reactivate these silenced genes.

If these demethylating agents prove as effective as Gonzalgo believes they will — if they manage to put the bullets back in the gun — he hopes to use them in clinical trials to help men with recurrent or metastatic prostate cancer.