Scientists are exploring a new treatment for mesothelioma, a rare and aggressive cancer linked to asbestos exposure, by targeting a specific antioxidant called PRX3. This enzyme helps tumor cells survive by neutralizing harmful molecules known as reactive oxygen species. In an early clinical trial, an experimental drug showed promise, controlling disease progression in 67% of patients and offering better survival outcomes than current treatments. Mesothelioma affects around 30,000 people worldwide each year, with most patients surviving only about 12 months after diagnosis and a five-year survival rate of roughly 10%. Many of these patients are men who previously worked in industries such as shipbuilding, oil refining, and asbestos manufacturing. Traditionally, cancer treatments using antioxidants aim to increase their levels to protect healthy cells. However, researchers at the University of Vermont (UVM) took a different approach by blocking PRX3, an antioxidant enzyme found inside mitochondria, the energy-producing parts of cells. When PRX3 is blocked, hydrogen peroxide—a harmful byproduct—builds up inside the mitochondria of cancer cells, leading to their destruction. Cancer cells are especially vulnerable to this strategy because they naturally produce more reactive oxygen species than normal cells, making them more susceptible to damage from hydrogen peroxide accumulation. The experimental treatment, developed by RS Oncology, is based on discoveries made at UVM and uses thiostrepton, a naturally occurring antibiotic, to disable PRX3. The drug is delivered directly into the chest through a catheter that many mesothelioma patients already have due to pleural effusions, a condition where fluid builds up between the lungs and chest wall. About 90% of mesothelioma patients develop pleural effusions. Delivering the drug locally allows doctors to focus the medication on the tumor while minimizing its spread throughout the body. Early trial results showed the treatment was generally well-tolerated, and patients in the study lived longer than those receiving standard care. The phase one study confirmed the drug was safe at a dose of 90 milligrams, with no deaths linked to the treatment. Researchers also found that the drug was successfully targeting PRX3 in human tumor tissue, confirming that the mechanism observed in laboratory studies also works in people. While the average progression-free survival was 4.2 months—similar to existing treatments—researchers were more encouraged by the overall survival rate. Among the 15 patients in the trial, survival outcomes were better than what is typically seen with current therapies. The research is now expanding in multiple directions. Scientists from UVM and RS Oncology, along with institutions in the UK such as the University of Leicester, are working on second-generation PRX3 inhibitors that are more soluble and could potentially be taken as oral tablets. This could make the treatment easier to use and possibly extend its application to other cancers. At UVM, lead researcher Gibson is continuing her work as a postdoctoral researcher, focusing on the potential of thiostrepton in treating other types of cancers, including peritoneal malignancies, gastric cancer, and other gastrointestinal cancers.