New mesothelioma treatment turns cancer’s defense into its weakness

A rare cancer tied to past industrial work has long left patients with few options and little time. Mesothelioma, most often caused by asbestos exposure, develops slowly and strikes decades later. By the time symptoms appear, the disease is often advanced. Survival averages about one year, and long-term outcomes remain poor.

Now, new research by the University of Vermont offers a different approach. Instead of protecting cells from damage, scientists are turning cancer’s own survival system against it. Early clinical results suggest the strategy may slow disease and extend lives.

Mesothelioma affects about 30,000 people worldwide each year. Many patients worked in shipbuilding, oil refining, or construction, where asbestos exposure was common.

Current treatments, including chemotherapy and immunotherapy, provide limited benefit. Most patients face a median survival of around 12 months. The five-year survival rate is near 10 percent.

“It’s a disease of a significant unmet medical need,” said Brian Cunniff, a professor at the University of Vermont.

Researchers have spent years searching for better treatments. Many past efforts focused on reducing harmful molecules inside cancer cells. This new study takes the opposite approach.

Cancer cells grow quickly and consume large amounts of energy. This process produces unstable molecules called reactive oxygen species. These molecules can damage cells if they build up.

To survive, tumor cells increase their defenses. They produce antioxidant enzymes that neutralize these harmful compounds. One key enzyme is called peroxiredoxin 3, or PRX3.

PRX3 works inside mitochondria, the parts of cells that produce energy. It removes hydrogen peroxide, a damaging molecule that forms during metabolism.

Scientists realized that mesothelioma cells depend heavily on this system. Without it, the cells could be overwhelmed by their own stress.

The idea was simple but bold. Instead of reducing oxidative stress, increase it. Block PRX3 and allow harmful molecules to accumulate. Push the cancer cells past their limit.

To test this idea, researchers removed PRX3 from mesothelioma cells in the laboratory. The results were immediate.

Cells without PRX3 grew more slowly. Their ability to multiply dropped sharply. Energy production declined, and oxidative stress increased.

In animal studies, the effect was even more dramatic. When these altered cells were introduced into mice, they failed to form tumors.

The findings showed that PRX3 is not just helpful for cancer cells. It may be essential for their survival.

Scientists also tested whether removing PRX3 would harm healthy tissue. Earlier studies in mice showed no major problems when the enzyme was absent.

Victoria Gibson, a research scientist involved in the study, addressed a common concern. “People will come up to us at conferences and state that you can’t target the mitochondria because they’re too important,” she said. “The evidence—that you can knock out PRX3 in mice and there’s no adverse phenotype— supports our approach.”

Building on these findings, researchers developed a drug to block PRX3. The treatment uses thiostrepton, a naturally occurring antibiotic, as its active component.

The drug, known as RSO-021, was created through a collaboration between the University of Vermont and RS Oncology. The goal was to translate lab discoveries into patient care.

The treatment is delivered directly into the chest cavity. This area often fills with fluid in mesothelioma patients, a condition called pleural effusion. Delivering the drug locally concentrates it at the tumor site while limiting effects on the rest of the body.

A phase one clinical trial tested the drug in 15 patients with relapsed mesothelioma. These patients had already received standard treatments.

The primary goal was to assess safety. At a 90 milligram dose, the drug was well tolerated. No deaths were linked to the treatment.

Researchers also looked for signs of effectiveness. The results were encouraging.

Disease progression was controlled in 67 percent of patients. In some cases, tumors shrank. Overall survival appeared longer than expected compared with standard therapies.

Progression-free survival averaged about 4.2 months, similar to existing treatments. However, the survival data stood out.

“Our overall survival data is very promising and will hopefully persist with additional patients,” Cunniff said.

The treatment works by disrupting the cancer cell’s ability to manage stress. When PRX3 is blocked, hydrogen peroxide builds up inside mitochondria.

This buildup damages the cell and triggers its death. Because cancer cells already produce high levels of reactive oxygen species, they are more vulnerable than normal cells.

The study also suggests another effect. The drug may help activate the immune system.

“Our drug has both cytotoxic activity, it can kill the tumor cells, but it also has immunomodulatory capacity where it can modulate the immune system to now manage the tumor,” Cunniff said.

This dual action could make the therapy more powerful than treatments that target only one pathway.

While the results are promising, not every patient responded equally. Some tumors showed strong sensitivity to the drug, while others did not.

Researchers identified a possible reason. A protein called SLC7A11 helps cells produce additional antioxidants. Tumors with higher levels of this protein were more resistant.

By increasing their defenses, these cells could survive even when PRX3 was blocked.

To overcome this, scientists tested combination treatments. When they paired the PRX3 inhibitor with a drug that blocks SLC7A11, cancer cell death increased significantly.

This approach targets multiple defense systems at once. It may improve outcomes in future trials.

The work is continuing on several fronts. A phase two clinical trial has already been completed, and results are expected soon.

Researchers are also developing new versions of the drug. These next-generation compounds may be more soluble and easier to deliver, possibly as oral medications.

The team is exploring whether the approach can treat other cancers. Early efforts focus on abdominal tumors, including gastric cancer and peritoneal mesothelioma.

“We believe this mechanism could be applicable to other cancers,” Cunniff said.

For Gibson, the work carries personal meaning. She recalled a moment that brought the research into focus.

“We just work in a lab all day working with cells,” she said. “And the fact that we’re making an impact on people, that they’re wanting to be on this clinical trial, just was amazing to me.”

This study offers a new direction for cancer treatment. By targeting how cancer cells manage stress, it opens a path that differs from traditional therapies.

For patients with mesothelioma, the approach could provide longer survival and better disease control. Local delivery of the drug may also reduce side effects compared with systemic treatments.

The research may extend beyond one disease. Many cancers rely on similar antioxidant systems. Targeting these pathways could lead to broader therapies.

The findings also highlight the importance of understanding tumor biology. Identifying markers such as SLC7A11 may help doctors choose the right treatment for each patient.

In the long term, combining therapies that target multiple survival systems could improve outcomes further. This strategy may help overcome resistance and make treatments more effective.

Research findings are available online in the journal Nature Communications.

The original story "New mesothelioma treatment turns cancer’s defense into its weakness" is published in The Brighter Side of News.

Like these kind of feel good stories? Get The Brighter Side of News' newsletter.