Viral infections and space travel similarly trigger inflammation and the enzymes APOBEC3C and ADAR1; researchers are developing ways to inhibit them as a means to potentially lower cancer risk for both astronauts and people on Earth.

Researchers at UC San Diego Health and University of California San Diego School of Medicine are working to understand what pushes pre-cancer stem cells to transform into cancer stem cells and are developing ways to stop that switch.

Their latest study, published January 26, 2021 in Cell Reports, is the first to show that, in response to inflammation, two enzymes called APOBEC3C and ADAR1 work together to fuel the transition from pre-cancer stem cells to cancer stem cells in leukemia. Both APOBEC3C and ADAR1 are activated by inflammatory molecules, especially during the body’s immune response to viruses.

The researchers also found they can prevent the formation of leukemia stem cells in the laboratory by inhibiting ADAR1 with fedratinib or ruxolitinib, two existing medications for myelofibrosis, a rare bone marrow cancer.

«APOBEC3C and ADAR1 are like the Bonnie and Clyde of pre-cancer stem cells — they drive the cells into malignancy,» said co-senior author Catriona Jamieson, MD, PhD, Koman Family Presidential Endowed Chair in Cancer Research, deputy director of Moores Cancer Center, director of the Sanford Stem Cell Clinical Center and director of the CIRM Alpha Stem Cell Clinic at UC San Diego Health.

Jamieson’s team has long studied ADAR1, an enzyme that edits a cell’s genetic material to control which genes are turned on or off at which times, and its role in leukemia stem cells. They also previously found that high ADAR1 levels correlate with reduced survival rates for patients with multiple myeloma.

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Materials provided by University of California — San Diego. Original written by Heather Buschman, PhD. Note: Content may be edited for style and length.