MU researchers develop powerful cancer treatment

The treatment is thousands of times more powerful than what is currently in use.

A team of MU researchers is fueling the fight against cancer with a new treatment, which is currently stronger than anything on the market.

“While we improved the activity of the structure tenfold, that structure was already an exceptionally potent experimental drug,” assistant professor of chemistry Mark Lee said. “These drugs are literally many of thousands of times more potent than the drugs used in today’s hospitals.”

The researchers used molecules known as carboranes to replace part of the structure of inhibitors of an enzyme known as Nampt to make the enzyme more effective at attacking the cancer cells.

“Carboranes were discovered in the mid-‘50s and were actually developed as rocket and jet fuel because they are highly energetic material,” Lee said. “For us, these clusters are a way to build better drugs for all sorts of diseases.”

Lee and his associates published an article with their findings in the Journal of Medicinal Chemistry.

“To our knowledge, these new carborane-based agents are now the most potent inhibitors reported to date for Nampt, an enzyme that has only recently come into focus as a central link connecting metabolism, cancer and inflammation,” according to the article.

This means that not only will the new drugs fight cancer, they will prevent it from returning to a patient and limit side effects from the treatment.

“Ideally, we’ll create new agents that are much more potent and selective for their targets so ideally what we want to do is minimize side effects,” Lee said.

These discoveries are still a long way from reaching hospital use, however.

“It takes a few years to collect all the information necessary for clinical trials, and it takes on average 10 to 15 years from discovery until proof, so it can take some time," Lee said. "We are not done by a long shot."

One of Lee’s co-authors on the paper, professor Shui Ye of the UM-Kansas City, explained the process behind this.

“Before these carborane-modified small chemical inhibitors are clinically applied to the treatment of human patients, more studies are needed to further test the effect of these compounds on cell metabolisms,” Ye said.

Lee said the team will proceed from pre-clinical work to animal testing, for which they will collaborate with others on campus and elsewhere.

“This team has been working on this project for the last three years, although testing phases just began in the last year,” Lee said. “The chemistry took longer than the testing. We synthesize our molecules from the ground up.”

If tests are successful, this new way of building drugs may soon become standard.

“It is highly likely that carborane-modified inhibitors will replace (the current structures) as a less toxic alternative to open the new window for cancer therapy down the road,” Ye said.

Though the process will be complicated, Lee said he is hopeful for the future.

“In terms of what we’ve shown, this is a route to better drugs,” he said. “We can absolutely kill cancer, the challenge is keeping the patient healthy while we do it.”

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