A groundbreaking study from the University of Vermont has revealed a novel approach to treating mesothelioma, a deadly cancer caused by asbestos exposure, offering new hope to patients with limited options. Traditionally, mesothelioma treatment relies on immunotherapy and chemotherapy, which provide only modest survival benefits and often leave patients with a median survival of just 12 months. The innovative strategy, recently published in Nature Communications, tackles the disease by exploiting a tumor’s own biochemical vulnerabilities, potentially reshaping future cancer therapies.
The key lies within the mitochondria of tumor cells, where high levels of reactive oxygen species (ROS) accumulate as a result of rapid metabolism. Tumors protect themselves by producing antioxidant enzymes, including peroxiredoxin 3 (PRX3), which detoxifies harmful molecules to maintain cellular survival. Contrary to prior attempts aiming to increase antioxidants to slow tumor growth, the UVM team, led by Professor Brian Cunniff and postdoctoral scientist Victoria Gibson, chose to inhibit PRX3, saturate the tumor with oxidative stress, and induce cell death.
The drug, RSO-021, developed in collaboration with RS Oncology LLC, uses thiostrepton, a naturally occurring antibiotic, to disable PRX3. This inhibition leads to an accumulation of hydrogen peroxide in the mitochondria, triggering apoptosis selectively in cancer cells due to their elevated ROS production. Laboratory experiments demonstrated that removing PRX3 crippled mitochondrial function, arrested tumor growth, and prevented tumor formation in animal models, without adverse effects in healthy mice—addressing common concerns about targeting mitochondria.
A phase one clinical trial conducted in the UK enrolled patients with relapsed mesothelioma, delivering the drug directly into the chest cavity via a catheter. This local administration concentrates the therapy at the tumor site while limiting systemic toxicity. The trial met its safety endpoints, showed disease stabilization in 67% of patients, and, notably, indicated improved overall survival compared to existing treatments—a promising sign of clinical efficacy.
Beyond its cytotoxic effects, preliminary data suggest RSO-021 may also activate the immune system, potentially enhancing the body’s own response to tumors. These dual effects mark a significant advance in cancer therapeutics, blending targeted molecular attack with immunomodulation.
The success of the phase one trial has propelled the research into phase two, with results anticipated later this year. Meanwhile, efforts are underway to develop second-generation PRX3 inhibitors with improved solubility and oral bioavailability, facilitating broader applications across other cancer types. Victoria Gibson continues her work at UVM, expanding investigations into peritoneal and gastrointestinal malignancies.
This paradigm-shifting approach offers a beacon of hope for mesothelioma patients and exemplifies how challenging prevailing cancer treatment dogma can unlock new avenues for therapy with potential widespread impact.
Subject of Research: People
Article Title: Preclinical characterization and phase 1 clinical testing of targeting mitochondrial peroxiredoxin 3 in cancer
News Publication Date: 14-Jul-2026
Web References: http://dx.doi.org/10.1038/s41467-026-75153-y
Image Credits: Joshua Brown/UVM
Keywords: Mesothelioma, PRX3, reactive oxygen species, thiostrepton, mitochondria, cancer therapy, clinical trial, oxidative stress, immunomodulation
