University research tracks source of cancer mutation

Researchers look to target enzymes that help cancer fight treatment

by Keaton Schmitt

A previously unknown molecule in roughly half of the world’s population that helps cancer fight treatment was recently found through University of Minnesota research.

Late last month, a University lab published a study which found an enzyme — A3H-I — that mutates cancer. A second study, published Friday, shows a similar molecule, A3B, which heavily mutates cancer cells, and correlates with bad medical outcomes.

When cancer has more mutations, it becomes better able to adapt to treatment and resist drugs.

In the second study, high amounts of A3B cut treatment’s effective time in half, said Douglas Yee, director of the Masonic Cancer Center and author on the second study.

The additional mutations give cancer cells more chances to develop traits that could fight drugs or the body, said Reuben Harris, professor in the Department of Biochemistry, Molecular Biology and Biophysics, and author on the studies.

More mutations could also give cancer a higher chance of spreading in the body, Yee said. Changes from mutation to the cancer cells could let them travel through the body more easily.

“If the tumor’s evolving at a faster rate, the likelihood of those tumors becoming resistant to whatever drug we throw at [it] will be much higher,” Harris said.

Cancer treatments often grow less effective over time, Yee said. If cancer mutation could be slowed down, doctors would be able to better treat patients, even without new cancer-killing drugs.

“Cancer is a disease of mutation; if there’s no mutations there’s no cancer,” Harris said.

This adaptation to treatment is a common problem in patients, said David Largaespada an associate director for basic science at the MCC.

Increasing drug resistance in cancer was recently picked by the Blue Ribbon Panel Cancer Moonshot — a national group of experts created to study cancer — as an important area where future research could find a solution.

Researchers found A3B causes mutations in cancer before, but about half of the world’s population lacks A3B and still has highly-adaptive cancer.

Harris said the team found those who lack A3B have A3H-I, which takes over in the absence of A3B and makes it easier for cancer to mutate. Drugs that inhibit A3H-I could let patients survive longer on conventional treatments.

If cancer could be continually suppressed without symptoms, it could be treated like a chronic disease, Yee said. Suppression of these enzymes could let doctors make cancer manageable instead of searching for a one-off “cure.”

“If I had a therapy that your quality of life and quantity of life would not be affected … that’s functionally a cure,” Yee said.

The lab is now working on making a drug to fight the enzymes, Harris said. Because the molecules are so similar, it’s likely a drug designed to inhibit one will also stop the other.

“Now that we know the targets … that are causing these mutations in cancer, we can target our therapies,” he said.

Currently, there are no drugs available that suppress cancer adaptation.