New "Prodrug" That Kills Cancer Without Damaging Healthy Cells

New Prodrug That Kills Cancer Without Damaging Healthy Cells

In a trial on mice, US researchers found that an enhanced medication kills cancer cells without producing harm. Researchers from Johns Hopkins Medicine in the US have improved an anti-cancer medicine to more effectively target cancer cells while sparing healthy tissues any harm.

This kind of focused strategy is known as a "prodrug" by scientists: a drug created to only release its payload in the specified region of the body...

People with advanced solid tumors are participating in early-stage clinical studies for the prodrug DRP-104, which was discovered and described in Science Advances. The prodrug preferentially destroyed cancer cells while sparing healthy cells, including those in the stomach, according to recently published research in mice.

"Our goal was to enhance a cancer treatment that had been utilized in the past but was too dangerous for clinical development. We adopted a prodrug strategy to achieve this. Our strategy is distinctive in that we used a cutting-edge chemical formulation to produce a prodrug that is simultaneously bio-activated in cancer cells and bio-inactivated in healthy tissues. Dr. Barbara Slusher, professor at the Johns Hopkins University School of Medicine and director of the Johns Hopkins Drug Discovery Program, said...

This effective class of medications may now be reevaluated safely in individuals thanks to the payload's selective targeting of cancer cells.

The newly altered prodrug makes use of glutamine, a crucial component of proteins, lipids, and nucleotides as well as a source of energy. "Glutamine addiction" describes the extreme glutamine consumption by rapidly expanding cancer cells.

Associate Professor of Neurology and Pharmacology Dr. Rana Rais noted that "DRP-104 is a tumor-targeted prodrug of the glutamine mimic drug termed 6-Diazo-5-Oxo-L-norleucine (DON), which inhibits several glutamine-utilizing enzymes in cancer cells."

The researchers didn't start working on this potential class of medications again until they decided to change DON's chemical composition.

As detailed by Slusher, "We added chemical groups, called promote ties, to DON that kept it inactive in the body up until it reached cancer, when the promote ties were snipped off by enzymes that are plentiful in the tumor."

Since DON was customized to its primary target (tumor), it had less of an effect on healthy cells elsewhere.

In the latest research, mice with tumor implants were given both the standard DON medication and the enhanced DRP-104 medication. Researchers discovered 11 times more active medicines in the tumor of DRP-104-treated animals than they did in the gastrointestinal system. Both treatments totally eliminated the tumor, however, DON was more harmful to the mice's intestines than DRP-104.

According to Slusher, the Johns Hopkins Drug Discovery lab is aggressively searching for more medications that have failed clinical trials due to toxicity issues. They want to use the same prodrug design for developing medications for different illnesses.