A new study suggests that PARP inhibitors may help target cancer cells in mesothelioma patients, offering hope for more effective treatment options.

Scientists think they may have finally found a way to slow the spread of malignant mesothelioma, a rare but unusually aggressive type of cancer with a low long-term survival rate.

Mesothelioma, sometimes termed “malignant mesothelioma,” can form in your mesothelial membrane. Your mesothelial membrane lines several of your body’s largest cavities and houses many of its most important organs.

Mesothelioma usually first appears in the pleural tissue surrounding your longs, but it is sometimes diagnosed in the abdomen, heart, and testicles, too. It can be caused by a rare genetic disorder, but the overwhelming majority of cases can be attributed to asbestos exposure.

“We have shown for the first time that this kind of drug can improve progression-free survival for mesothelioma patients compared with their usual treatment in the NHS,” Griffiths said, referring to the United Kingdom’s national healthcare system. “This gives enormous hope to those patients and their families and means we can now carry out further research to find out more about how these treatments could be tailored and enhanced to stimulate an ever-better response in more people.”

Mesothelioma is a challenging diagnosis.

Even compared to other cancers, mesothelioma is aggressive: doctors know they can’t keep pace with its spread and will often only try to treat symptoms instead of the cancer itself.

But a recent development out of the United Kingdom could provide unprecedented hope for people diagnosed with mesothelioma. According to the results of a recent study, the use of a certain type of drug—called PARP inhibitors—could prevent cancerous tumors from growing larger and metastasizing to other parts of the body. In some cases, patients who took PARP inhibitors have survived for years longer than expected.

Asbestos and Mesothelioma

What exactly is asbestos?

Asbestos is a naturally-occurring mineral found across the United States. It is comprised of small fibers, which are fireproof, corrosion-resistant, and extraordinarily durable. These properties led to asbestos being used to reinforce a wide variety of products and materials, ranging from the insulation aboard U.S. Navy aircraft carriers to automotive brakes and cigarette filters.

The seemingly incredible utility of asbestos also poses a danger. Asbestos isn’t indestructible: asbestos-containing materials can flake and chip during production, assembly, or repair, and they can break down over long periods of time, too. Crumbled asbestos, called “friable asbestos,” is comprised of tiny, microscopic fibers—fibers that are small enough to be inhaled without ever noticing.

Latency: Asbestos fibers damage your body over time.

Once inside the body, asbestos can work its way into the respiratory and begin wreaking havoc from the inside-out. Your body will recognize asbestos as an unwanted guest, and it may activate defense mechanisms in response. But with asbestos being so incredibly strong, your immune system will never, ever win its fight.

Instead, embedded fiber will remain in your pleural tissue forever. In some cases, it can scar your lungs and goad your immune system into throwing everything it has at it. Over time, this can result in chronic inflammation, which is closely associated with an increased risk for cancer.

Asbestos is still a problem, in the environment and in peoples’ bodies.

Asbestos today is tightly regulated at the state and federal level, but, before the 1980s, tens of millions of Americans were exposed to asbestos on a daily basis, whether at work or in the home. Decades later, many of these same people have been diagnosed with asbestos-related illnesses, including asbestosis, pleural disease, and mesothelioma.

Mesothelioma isn’t usually noticeable until it has already progressed to an advanced state—something that may not happen for a very, very long time. Consequently, people who worked with asbestos in the past often have no noticeable symptoms until they’re in their 60s or 70s.

Once identified, mesothelioma is notoriously difficult to treat, with fewer than 10% of patients living more than 5 years past their date of diagnosis. Treatment is typically geared toward relieving unpleasant symptoms, but chemotherapy and other care can still be physically exhausting and emotionally draining.

The NERO Trial

Earlier this year, researchers at the University of Leicester and the Cancer Research UK Clinical Trials Unit, both located in the United Kingdom, announced the results of a long-term study: the NERO trial.

The NERO trial was designed to assess the efficacy of a class of drugs known as PARP inhibitors in the treatment of mesothelioma. In general, PARP inhibitors work by blocking a protein responsible for the repair of damaged DNA in cells. By blocking this protein, cancer cells can’t repair themselves. Unable to reproduce, they eventually die.

PARP inhibitors are already believed to improve survival rates among patients diagnosed with certain typers of breast and ovarian cancer, but past studies had indicated it was ineffective for mesothelioma.

During the NERO trial, researchers collaborated with 11 hospitals across the United Kingdom to provide experimental PARP inhibitor therapy to patients with mesothelioma. About 88 people took part in the trial; all of them had attempted conventional treatment and failed.

PARP Inhibitors as a Treatment for Mesothelioma

After the NERO trial came to an end, researchers evaluated their findings and came to a surprising conclusion: mesothelioma patients who had been administered a PARP inhibitor called niraparib had, on average, a 27% reduction to the risk of dying or the cancer spreading.

What are PARP Inhibitors?

In an abstract summarizing the results of Phase II of the NERO trial, researchers found that a significant percentage of patients receiving niraparib in combination with another drug, dostarlimab, experienced benefits including:

Partial remission
Reduced tumor growth
Lower chances of disease progression

One of the participants in the trial, James Fox of Dorset, was diagnosed with mesothelioma in 2018. At the time, doctors told him that he had less than a year to live. Having already other treatment options, he enrolled in the NERO trial.

Mesothelioma has an average 5-year survival rate of just 5%.

Nearly seven years later, Mr. Fox is still alive.

Now, he says that the experimental treatment has surpassed all his expectations.

“It’s dramatic, the improvement, I don’t think this could have possibly happened without this particular drug, without being offered it,” he told the BBC. “It must be the drug that’s been keeping me fit and alive, so I’m very grateful for that.”

Professor Gareth Griffiths, the director of the Southampton Clinical Trials Unit and co-lead of the trial, told the BBC that niraparib’s apparent success is “a significant step forward” for mesothelioma research.