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ETSU student working on prodrug to treat prostate cancer

Jennifer Sprouse • Dec 3, 2012 at 1:49 PM

Cancer research is being conducted all around the country, but in our own backyard discoveries related to the termination of prostate cancer cells are in the works.

Christopher McGoldrick, a doctoral candidate in East Tennessee State University’s Department of Biomedical Sciences at the James H. Quillen College of Medicine and graduate research assistant under the faculty supervision of Dr. William Stone, has been working since he was an undergraduate in 2007 to research a prodrug that would be used in chemotherapy to help treat prostate cancer.

McGoldrick said the initial approach to this project, “Identification of Oxidized Protein Hydrolase as a Prodrug Target in Prostate Cancer,” was to look for a universal treatment option.

“What we wanted to do was to develop a new therapy that would not impact the patient’s quality of life so much by not damaging those normal cells and specifically killing the cancer cells. To do that, we’ve kind of followed the trails of another research group from the 1990s, a Japanese group. What they looked at were esterase levels, which is an enzyme that’s found in all cells, but they found that these were elevated higher in cancer cells, so this made a good target to affect cancer cells,” he said.

Esterase is an enzyme that breaks down other compounds, which McGoldrick said would make a good activator for drugs because they would break an inactive drug and make it active.

McGoldrick has been using what is known as a prodrug, which starts out as an inactive precursor with no effect on normal cells or cancer cells until it is administered to a patient.

“When the drug enters a cell, it’s acted on by those esterases, which activates it and because the cancer cells have so much higher levels of that esterase the drug is activated more in the cancer cell and then that leads to the cancer cells’ death without having much effect at all on the normal cells,” he said. “Probably the biggest step in all of this was actually identifying the one esterase that the drug is activated by and that’s called oxidized protein hydrolase.”

McGoldrick said they’ve been testing the prodrug on cell cultures and the next step would be testing on animal models and performing the treatments.

“We have a very good proof of concept of the way this prodrug could work to kill cancer, so even if this particular drug doesn’t turn out to be effective in animal models our underlying thought about how this works, I think, is sound. This may lead to other new drugs, more efficient drugs, that use the same mechanism to be activated, so I think we’ve opened up a new little area for drug development,” McGoldrick said. “We’re still at the very beginning of this for the most part, but ... what we are seeing so far is very encouraging.”

And while the prodrug is specifically targeting prostate cancer cells, he said they’ve also gathered evidence it could possibly work with other forms of cancer.

“We’ve started to look at melanoma, pancreatic cancer, colon cancer and we’re seeing similar results so far, so it looks like this might be kind of a good treatment for cancers in general,” McGoldrick said.

The project is supported by an ETSU Graduate Studies Research Grant.

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