An experimental drug developed from a natural antibiotic has controlled disease progression in 67% of relapsed mesothelioma patients during a phase one clinical trial, targeting a protective antioxidant enzyme inside cancer mitochondria to overcome a disease with a median survival of about 12 months.
How Mesothelioma Develops and Why Treatment Remains Limited
Malignant mesothelioma is a rare and aggressive cancer most often linked to exposure to asbestos at work, in older buildings, or through living with someone who handled the minerals. When long, thin asbestos fibers are inhaled, they become trapped in the lungs and trigger chronic inflammation that can eventually lead to cancer decades later. About 30,000 people worldwide receive a diagnosis every year.
Patients face severe treatment hurdles. While immunotherapy and chemotherapy help some individuals, options remain restricted, and the disease is extremely difficult to control. Affected individuals—frequently men with work histories in shipbuilding, oil refining, and asbestos manufacturing—face a median survival of about 12 months. The five-year survival rate sits at approximately 10 percent.
Reversing Antioxidant Logic to Target Cancer’s Powerhouses
Researchers at the University of Vermont challenged traditional antioxidant strategies in cancer therapy. While past clinical trials tested whether increasing antioxidants could fight tumors by reducing unstable molecules known as reactive oxygen species,
many of those efforts failed or suggested that boosting antioxidants actually aided tumor growth.
Cancer cells generate high levels of reactive oxygen species due to their active metabolisms. To survive that internal stress, tumor cells increase their production of protective antioxidant enzymes. One key enzyme is peroxiredoxin 3, or PRX3, which operates directly inside the mitochondria that generate cellular energy. Instead of supplying more antioxidants, the research team focused on depriving cancer cells of PRX3 to let oxidative damage build until cells die.
From University Discoveries to Clinical Trials With RSO-021
The experimental treatment uses thiostrepton, a naturally occurring antibiotic designed to disable PRX3 and cause hydrogen peroxide to accumulate inside tumor mitochondria. Laboratory experiments showed that when researchers deleted PRX3 from mesothelioma cell lines, mitochondrial function declined, cell growth slowed sharply, and the cells could no longer form tumors in animal tests. Additional research confirmed that knocking out PRX3 in healthy mice produces no adverse phenotype.
“The evidence — that you can knock out PRX3 in mice and there’s no adverse phenotype — supports our approach.”
Victoria Gibson, University of Vermont
Scientific groundwork for the treatment began around 2015 at the University of Vermont’s Cancer Center. Investigators helped establish RS Oncology, LLC, a private pharmaceutical company created to move the discoveries toward human testing. Brian Cunniff serves as the company’s chief science officer. The team transformed thiostrepton into a clinical formulation named RSO-021. Between 2022 and 2023, researchers tested RSO-021 in a phase one clinical trial sponsored by RS Oncology in the United Kingdom, where the experimental drug controlled disease progression in 67% of participants with relapsed mesothelioma, shrank tumors in some patients, and was generally well tolerated.
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