‘Game changer' drug turns cancer's defenses against itself
By Stephen Beech
A new drug that turns cancer's own defenses against itself has shown "promise" in treating one of the deadliest forms of the disease.
Doctors have been able to control the disease in two out of three mesothelioma patients using the "game changer" treatment that attacks cancer's energy system.
Mesothelioma is a rare but aggressive cancer, usually caused by exposure to asbestos.
Around 30,000 people are diagnosed worldwide with mesothelioma each year.
Current treatments - immunotherapy and chemotherapy - offer limited benefit.
Patients - often men who worked in shipbuilding, oil refining, and asbestos manufacturing - face an average survival of 12 months, and the five-year survival rate is just 10%.
Now an international research research team, led by scientists from the University of Vermont (UVM) in the United States, have developed a "counterintuitive" new approach to treating mesothelioma - and perhaps other cancers too.
Study leader UVM professor Brian Cunniff said: "It's a disease of a significant unmet medical need."
In a "phase one" clinical trial conducted in the United Kingdom, people with relapsed mesothelioma were given the new drug and it controlled disease progression in 67% of patients and in some the tumors got smaller.
The drug was well tolerated and the critically ill patients lived longer than patients given the standard treatments, according to the findings published in the journal Nature Communications.
Cunniff explained that, like many cancers, mesothelioma tumors generate elevated levels of "reactive oxygen species" - unstable and damaging molecules that are a byproduct of rapid tumor cell metabolism.
To survive under those conditions, tumor cells ramp up production of antioxidant enzymes, including one called peroxiredoxin 3, or PRX3, in the cell's "powerhouses" - the mitochondria - that protect tumor cells from damaging molecules.
The research team flipped the conventional logic of cancer treatment.
For years, clinical trials attempted to increase antioxidants to combat cancer, reasoning that lowering reactive oxygen species would slow tumor growth.
Those trials largely failed, and some showed that increasing antioxidants promoted tumor growth.
The Vermont team took the opposite approach: inhibit PRX3, overwhelm the tumor cell with oxidative stress, and kill it.
The trial drug developed by pharmaceutical firm RS Oncology, based on the team's discoveries, uses a naturally occurring antibiotic, called thiostrepton, to disable PRX3.
It causes a buildup of hydrogen peroxide in the mitochondria of tumor cells and triggers their death.
Because tumor cells generate more reactive oxygen species than normal cells, the researchers say PRX3 turns over faster in tumor cells which increases selectivity to cancer cells rather than healthy ones.
When the team deleted PRX3 entirely in mesothelioma tumor cell lines, mitochondrial function decreased, cell proliferation slowed "dramatically" - and the cancer cells were unable to form tumors in animal tests.
Other research has shown that when PRX3 is knocked out in healthy mice, there were no adverse effects.
Study lead author UVM research scientist Victoria Gibson said: "People will come up to us at conferences and state that you can't target the mitochondria because they're too important.
"The evidence - that you can knock out PRX3 in mice and there's no adverse phenotype - supports our approach."
Cunniff said the drug is administered directly into the chest through a catheter already in place for patients who have "pleural effusions" - a buildup of fluid between the lung and chest wall that affects around 90% of mesothelioma patients.
The local delivery concentrates the drug at the tumor site.
The phase one trial met its requirements for safety and tolerability at a 90-milligram dose, with no patient deaths attributed to the drug.
Crucially, the team showed on-target engagement in patient tissue samples - confirming that the drug's mechanism of action, observed in cells and mice in the lab, also works in human tumors.
Progression-free survival averaged 4.2 months, comparable to current therapies.
More significantly, overall survival in the group of 15 patients was better than what is seen with existing treatments - a finding Cunniff describes as a potential "game changer."
He said: "Our overall survival data is very promising and will hopefully persist with additional patients."
The team's data also suggests the new drug may also help awaken the immune system to attack or slow the tumor.
Cunniff said: "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."
Phase two of the drug trial has now been completed, and results are expected to be presented at a global oncology meeting later this year.
The UVM and RS Oncology team, in collaboration with the University of Leicester and other institutions in the U.K., are now developing second-generation PRX3 inhibitors that are more soluble and potentially deliverable as an oral tablet.
They say this might allow the drug to be brought to market more easily and have application with cancer types beyond mesothelioma.
Cunniff said: "We believe this mechanism could be applicable to other cancers."
Gibson, a doctoral student, says the work is personal.
She said: "I've always just had a desire to help people because I feel like everyone has experienced cancer in their life, whether it's them, friends, or family members."
But when a family member called the lab hoping to enroll her dying father in the clinical trial, Gibson was caught off guard.
She added: "We just work in a lab all day working with cells.
"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."
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This story was originally published July 14, 2026 at 11:26 AM.