Mesothelioma is a rare and aggressive cancer that is most often linked to asbestos exposure. When asbestos fibers are inhaled, they can become trapped in the lungs, where they trigger chronic inflammation that may eventually lead to cancer decades later. About 30,000 people worldwide are diagnosed with mesothelioma every year.
Treatment options remain limited. Immunotherapy and chemotherapy can help some patients, but the disease is still extremely difficult to control. Patients, many of whom are men who previously worked in industries such as shipbuilding, oil refining, and asbestos manufacturing, have a median survival of about 12 months.
The five year survival rate is approximately 10 percent. "It's a disease of a significant unmet medical need," says Brian Cunniff, a professor at the University of Vermont. Now, research published in Nature Communications by Cunniff, UVM research scientist Victoria Gibson, and an international team of collaborators describes an unusual strategy that could offer a new way to treat mesothelioma and potentially other forms of cancer.
In a phase one clinical trial sponsored by RS Oncology, LLC, patients with relapsed mesothelioma received an experimental drug that controlled disease progression in 67% of participants. Tumors also shrank in some patients. The drug was generally well tolerated, and the critically ill patients in the trial lived longer than patients receiving standard treatments.
Turning Cancer's Protective System Into a Weakness Mesothelioma cells, like many cancer cells, produce unusually high levels of "reactive oxygen species," unstable molecules that can damage cells. These molecules are generated in part because tumor cells have highly active metabolisms. To survive that stressful environment, cancer cells increase production of antioxidant enzymes that help neutralize the damaging molecules.
One of those enzymes is peroxiredoxin 3, or PRX3, which operates inside mitochondria, the structures that produce much of a cell's energy. The UVM researchers decided to reverse the usual logic behind antioxidant-based cancer strategies. For years, scientists tested whether increasing antioxidants could help fight cancer by reducing reactive oxygen species.
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