Cellular process discovery may lead to new cancer treatments

A molecular geneticist at Montana State University has identified a cellular process once considered impossible: the creation of the amino acid cysteine inside living cells when their primary systems to produce it fail. The discovery, published May 21 in *Nature Chemical Biology*, could lead to new cancer treatments by targeting how cancer cells survive chemotherapy, radiation, or immune therapies. Cysteine is essential for cell survival, helping build proteins, defend against damage, and maintain cell structure through disulfide bonds. Scientists previously believed cells relied solely on a disulfide reductase system to split cystine, an oxidized form of cysteine, into usable cysteine. However, Ed Schmidt, a professor of genetics and development, found a backup system in mammalian cells that chemically severs an adjacent carbon-sulfur bond in cystine when the primary system fails. The discovery emerged over nine years, beginning in 2014 when genetically engineered mice lacking the two primary disulfide reductases in their livers unexpectedly survived. Schmidt and his team, collaborating with Peter Nagy from the Hungarian National Institute of Oncology, later determined the mice used an alternative pathway to produce cysteine. This backup system likely evolved in early multicellular ancestors to protect cells from electrophilic toxins found in food or the environment. The same pathway that protects normal cells from toxins may also shield cancer cells from therapies. Schmidt noted that disabling this defense mechanism in cancers could make them more vulnerable to treatments. The research suggests a potential new strategy for improving cancer therapy outcomes by targeting this previously unknown cellular process.