As reported on Vermont Biz, researchers at the University of Vermont (UVM) and biotechnology company RS Oncology have reported encouraging results from an early-stage clinical trial of a novel treatment for mesothelioma, a rare and highly aggressive cancer most commonly linked to asbestos exposure. The findings, published in Nature Communications, suggest that the therapy may not only slow disease progression but also extend patient survival while maintaining a favorable safety profile.
Mesothelioma remains one of the most difficult cancers to treat. Despite advances in chemotherapy and immunotherapy, patients typically face poor outcomes, with survival rates remaining low. The disease often appears decades after asbestos exposure, particularly among individuals who worked in industries such as shipbuilding, construction, oil refining, and asbestos manufacturing.
The new treatment takes an unconventional approach by targeting the cancer cells’ internal defense mechanisms rather than attempting to reduce harmful cellular stress. Cancer cells generate large amounts of reactive oxygen species—unstable molecules produced during rapid metabolism. To cope with this stress, tumors rely on protective antioxidant proteins, including an enzyme known as peroxiredoxin 3 (PRX3), which helps preserve mitochondrial function.
Instead of shielding cells from oxidative damage, the research team sought to disable this protective system. Their strategy uses a drug derived from thiostrepton, a naturally occurring antibiotic, to inhibit PRX3. Without the enzyme’s protection, toxic levels of hydrogen peroxide accumulate inside tumor cell mitochondria, leading to cancer cell death. Because cancer cells experience greater oxidative stress than healthy cells, they appear to be more vulnerable to this targeted approach.
Laboratory studies provided strong support for the concept. When researchers eliminated PRX3 in mesothelioma cell lines, the cancer cells grew more slowly, showed impaired energy production, and lost their ability to form tumors in animal models. Previous research also indicated that healthy mice can function normally without PRX3, suggesting that targeting the enzyme may spare normal tissues from significant harm.
To move the discovery from the lab to patient care, UVM researchers worked with RS Oncology to develop a clinical formulation known as RSO-021. A Phase 1 trial conducted in the United Kingdom between 2022 and 2023 enrolled patients with relapsed mesothelioma. The drug was delivered directly into the chest cavity through catheters already used to manage pleural effusions, a common complication affecting most mesothelioma patients. This localized administration allows higher concentrations of the drug to reach tumors while reducing exposure elsewhere in the body.
The trial demonstrated that the treatment was safe and generally well tolerated at the tested dose. No deaths were attributed to the drug, and tissue analyses confirmed that it was successfully reaching and affecting its intended biological target within tumors.
Clinical outcomes were particularly encouraging. Disease progression was controlled in approximately two-thirds of participants, and some patients experienced measurable tumor shrinkage. While progression-free survival was similar to existing therapies, researchers reported that overall survival appeared better than expected when compared with current standards of care. Investigators view this finding as one of the most promising aspects of the study.
The therapy may offer an additional benefit beyond directly killing cancer cells. Early evidence suggests that it could also help stimulate immune activity against tumors, potentially creating a dual mechanism that both destroys cancer cells and enhances the body’s ability to keep the disease under control.
A Phase 2 trial has already been completed, and researchers expect to share those results at a major international oncology conference later this year. Meanwhile, the team is working on next-generation PRX3 inhibitors that are more easily absorbed and may eventually be available in oral form. Researchers are also exploring whether the same mechanism could be effective against other cancers, including abdominal mesothelioma, gastric cancer, and additional gastrointestinal malignancies.
For the scientists involved, the project represents more than a scientific achievement. It highlights the potential real-world impact of laboratory research, transforming discoveries made in cell cultures and animal studies into treatments that may improve outcomes for patients facing a disease with few effective options. If future trials confirm the early results, PRX3 inhibition could emerge as an important new strategy in cancer therapy, offering renewed hope to mesothelioma patients and potentially many others.
