A new experimental drug opens up promising prospects for treating mesothelioma, one of the rarest and most aggressive forms of cancer, after initial results showed its ability to slow the progression of the disease and reduce tumor size.
Mesothelioma is a rare cancer most often linked to exposure to asbestos fibers, which become lodged in the lungs and cause chronic inflammation that can develop into tumors years or even decades later. Around 30,000 people are diagnosed with this disease annually worldwide, with an average survival rate of less than one year and a five-year survival rate of only about 10%, even with chemotherapy and immunotherapy. (Asbestos fibers are very fine, naturally occurring mineral fibers that were once widely used in building materials and industry due to their high resistance to heat, fire, and chemicals.)
Researchers at the University of Vermont, in collaboration with an international team led by Professor Brian Conniff and researcher Victoria Gibson, adopted a different approach to cancer treatment. Instead of reducing oxidative stress within cells, which previous experiments using antioxidants had unsuccessfully attempted, the team focused on increasing this stress to force cancer cells to die.
Cancer cells produce large quantities of molecules known as reactive oxygen species (ROS), which are unstable substances resulting from the tumor's high metabolic activity. To protect themselves, these cells rely on an antioxidant enzyme called PRX3, found within the mitochondria, the cell's energy-producing organelles.
The researchers targeted this enzyme using a drug developed by RS Oncology based on discoveries at the University of Vermont. The drug contains the natural antibiotic thiostrepton, which disrupts the action of the PRX3 enzyme, leading to an accumulation of oxidative materials within cancer cells until they collapse and die.
This approach is characterized by targeting cancer cells to a greater extent than healthy cells, because tumors rely more heavily on the PRX3 enzyme to survive.
Laboratory experiments confirmed this hypothesis, as the deletion of the enzyme from mesoderm tumor cells led to a decrease in mitochondrial activity, a reduction in the cells' ability to proliferate, and their failure to form tumors in experimental animals.
Other studies have also shown that disabling the gene responsible for producing the enzyme in healthy mice did not cause significant side effects, which supports the safety of targeting this therapeutic pathway.
The treatment then moved to clinical trials, where researchers developed the compound into a drug called RSO-021, and its first clinical trial was conducted in the United Kingdom.
The study included patients with mesothelioma that recurred after receiving treatment
The drug was given directly into the chest cavity via a catheter in patients with pleural effusion, a condition in which fluid accumulates between the lung and the chest wall, affecting about 90% of mesothelioma patients.
The results showed that the drug was safe and well-tolerated, with no associated deaths. It also successfully controlled disease progression in 67% of patients, and tumors shrank in some.
The average progression-free survival time was 4.2 months, a rate comparable to current treatments, but the overall survival rate was better than expected, which the researchers described as an encouraging indicator worthy of further study.
Konev said: "The survival data are very promising, and we hope these results will be confirmed as the number of patients increases."
He added that the treatment not only kills cancer cells, but also appears to contribute to activating the immune system to attack and control the tumor.
The second phase of clinical trials has been completed, and the results are expected to be announced during a global oncology conference this year.
Meanwhile, researchers are working on developing a new generation of PRX3 inhibitors that can be taken orally in tablet form, making them easier to use and expanding their range of applications.
The team is also exploring the possibility of using this approach to treat other cancers, including malignant peritoneal tumors, stomach cancer, and various types of gastrointestinal cancers.
The study was publHished in the journal Nature Communications.
