Researchers at the University of Vermont, working with RS Oncology, have reported encouraging Phase 1 results for RSO-021, an experimental drug that fights malignant mesothelioma by disabling a defense the tumor relies on rather than attacking it directly. Mesothelioma cells run in a state of high oxidative stress and survive by producing large amounts of the antioxidant enzyme peroxiredoxin 3 (PRX3) inside their mitochondria. RSO-021, derived from the natural antibiotic thiostrepton, blocks PRX3, letting hydrogen peroxide build up until the cancer cell destroys itself, while sparing healthy tissue.
In the UK trial of 15 patients, delivering the drug directly into the chest cavity via catheter controlled disease progression in 67% of participants, with tumors shrinking in some cases and average progression-free survival of 4.2 months. Overall survival exceeded current standard treatments, and the drug was generally well tolerated. "Our overall survival data is very promising and will hopefully persist with additional patients," said Brian Cunniff, a UVM professor and chief science officer at RS Oncology, calling the results a potential "game changer."
Mesothelioma, an aggressive cancer linked to asbestos exposure, has long had few effective treatment options. A Phase 2 trial has already been completed, with results due at a global oncology meeting, and researchers are now developing second-generation oral PRX3 inhibitors that could extend the approach to other hard-to-treat cancers, including gastric and gastrointestinal malignancies.