Experimental Drug Shows Promise in Treating Mesothelioma

Researchers at the University of Vermont (UVM) and RS Oncology have reported progress in treating mesothelioma, an aggressive cancer often linked to asbestos exposure. A phase 1 clinical trial of an experimental drug managed to control the disease in 67% of participants. Patients with this cancer typically face a difficult prognosis, with a median survival of 12 months and a five-year survival rate of approximately 10%. Published in Nature Communications, the study suggests a new way forward for treating a condition that has long been difficult to manage.

Mesothelioma develops when asbestos fibers accumulate in the lungs, causing chronic inflammation and the eventual development of cancer. Historically, treatment options have been limited, as chemotherapy and immunotherapy often provide only modest benefits. Brian Cunniff, a professor at UVM, emphasized the significant unmet medical need for effective mesothelioma therapies. The UVM team concentrated their research on the PRX3 antioxidant enzyme, which cancer cells rely on to manage oxidative stress and survive in hostile environments.

In the clinical trial, patients with relapsed mesothelioma were treated with the experimental drug targeting PRX3. The results showed promising control of the disease, and some tumors shrank. The drug was well-tolerated, and patients experienced longer survival times than those receiving standard treatments. Researchers including Victoria Gibson aimed to take advantage of the cancer cells' reliance on antioxidant defenses, leading to increased oxidative damage and cell death.

The treatment uses thiostrepton, a natural antibiotic that inhibits PRX3. By blocking this enzyme, the drug allows hydrogen peroxide to build up within the cancer cells, which triggers their death. Laboratory studies showed that removing PRX3 from mesothelioma cell lines lowered mitochondrial function and stopped tumor growth in animal models. Notably, removing PRX3 in healthy mice did not cause adverse effects, supporting the safety of the method.

What began as research at UVM around 2015 has since evolved into the clinical drug RSO-021. Following laboratory results, the drug was tested in a phase 1 clinical trial in the UK between 2022 and 2023. These outcomes could lead to further clinical applications and research into similar strategies for other cancers, marking a development in medical oncology.