Working with scientists from Massachusetts-based biopharmaceutical company RS Oncology, researchers from the University of Vermont (UVM) have published promising Phase I clinical trial results showing that a new drug controlled mesothelioma progression in 67% of patients. The drug, called RSO-021, targets a key vulnerability in how tumor cells protect themselves, turning the cancer’s own energy-producing defenses against itself.
Drug Overwhelms Mesothelioma Cells with Oxidative Stress
To understand the UVM researchers’ approach, you need to know that mesothelioma is an extremely aggressive form of cancer, and as a byproduct of its rapid cell metabolism, its tumors generate elevated levels of unstable, damaging molecules called reactive oxygen species. To protect themselves from these molecules, mesothelioma tumor cells produce a protective enzyme called peroxiredoxin 3, or PRX3. While previous treatments have focused on directly fighting this defense, the new drug inhibits PRX3, allowing tumor cells to be overwhelmed and killed by the oxidative stress they produce themselves.
Writing in the journal Nature Communications, the team explains that RSO-021 uses a naturally occurring antibiotic called thiostrepton to disable PRX3. This causes a buildup of hydrogen peroxide in tumor cell mitochondria that triggers their death. When the team deleted PRX3 entirely in healthy mice, the animals showed no adverse effects, addressing a common concern about targeting mitochondria: the drug is selectively toxic to tumors while sparing healthy tissue.
Mesothelioma Survival Data Called “Very Promising”
The Phase I mesothelioma trial enrolled 15 patients with relapsed disease and no remaining treatment options. The drug was administered directly into the chest through a catheter, concentrating treatment at the tumor site while limiting systemic exposure. Progression-free survival averaged 4.2 months, comparable to current therapies, but overall survival in the cohort exceeded what is typically seen with existing treatments. All safety and tolerability requirements were met, with no patient deaths attributed to the drug. The drug may also help the immune system recognize and attack mesothelioma tumors.
Phase II trials have already been completed, and results are expected to be presented at a global oncology meeting later this year. Meanwhile, researchers are developing second-generation PRX3 inhibitors that are more soluble and potentially deliverable as an oral tablet, while expanding investigation into peritoneal malignancies and other gastrointestinal cancers—suggesting that a mesothelioma breakthrough may ultimately benefit patients with multiple difficult-to-treat cancer types.
If you or someone you love has been diagnosed with mesothelioma, groundbreaking research like this offers real hope. For information on other resources available to you, contact the Patient Advocates at Mesothelioma.net today at 1-800-692-8608.
