Mesothelioma Awareness Day: How research is tackling the deadly legacy of asbestos – Cancer Research UK (blog)

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The UK had a lot to do to pick itself up after the devastation of World War II. And asbestos, then a wonder insulation material, had a huge part to play.

Being both heat and fire resistant, asbestos was lapped up by manufacturing industries, and ploughed into everything from homes and their appliances to ships and cars.

Sadly, the microscopic fibres of asbestos that workers were breathing in would go on to cause a different kind of devastation in the years to come.

It wasn’t long before patterns of disease in these workers started to arouse suspicion, and in 1960 its link with a type of cancer called mesothelioma was first documented.

With cases of this disease rising in the UK, one of our scientists led research that showed there’s no such thing as a ‘safe’ level of exposure to asbestos (this blog post has the full tale).

That crucial work led to new laws protecting future generations from asbestos exposure – its use has been banned in the UK since 1999. But that’s not the end of the tale.

The UK still sees around 2,700 cases of mesothelioma each year, and the problem is far from limited to this country. Survival for the disease also remains stubbornly low, with few treatment options available.

So now, much like the early discoveries around asbestos and health, small pockets of the research community are chipping away at the scientific challenge of mesothelioma, and the best ways to tackle it.

What is mesothelioma?

Mesothelioma is a cancer that starts in the mesothelium – the delicate layers of cells that wrap around most of our internal organs. The majority of cases develop in the chest, called pleural mesothelioma, but some can occur in the abdomen, known as peritoneal mesothelioma.

The disease is much more common in men than women, with around 5 times as many men being affected in the UK each year. This is most likely because of exposure to asbestos in industries that have traditionally been more male-dominated. And the cases in women over the years are likely down to handling clothing contaminated with asbestos.

Asbestos fibres under the microscope. Asbestorama/USGS. Flickr/CC BY 2.0

Survival for mesothelioma depends on a number of factors, such as how ancient a person is when they develop the disease, their gender, and how far advanced the disease is when it’s diagnosed. But broadly speaking, the outlook in the UK is poor, with only around 5 in 100 men surviving their disease for 5 years or more, and 10 in 100 women.

Such low survival is partly down to the fact that many people are diagnosed late, when the disease has spread and become more hard to treat. That’s because early stages of the disease don’t really come with many symptoms, and some of the symptoms that might appear – like a persistent cough – could be tied to much less serious conditions.

Another reason for low survival, clarifies Professor Dean Fennell, a Cancer Research UK-funded expert on mesothelioma from the University of Leicester, is the lack of effective treatments.

“There has really only been one standard of care since 2003, which is based on chemotherapy,” he says.

So what’s going on to make treatments better?

Understanding mesothelioma biology

The more scientists know about a cancer, the more precise they can make treatments. And that’s what is going on right now with mesothelioma.

“Recently there have been some significant advances in our understanding of the biology of the disease,” says Fennell. “Perhaps some of the most significant are the discovery that immune ‘checkpoints’ may be a target.”

These ‘checkpoints’ refer to molecules in the body that are sensed by the immune system to prevent it from attacking healthy tissue or becoming out of control. But cancer cells can co-opt this system, using it to tell the immune system not to attack. That’s why scientists have developed immunotherapy drugs that target these checkpoints, called checkpoint inhibitors.

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  • Check out this video for more info on how checkpoint inhibitors work.

“We’re seeing the most rapid advances for mesothelioma in the immunotherapy space,” Fennell says. “A combination of checkpoint drugs is now being evaluated in a large global clinical trial – if successful it could have a huge impact by providing another treatment option.”

Fennell is among many others involved in clinical trials looking at different immunotherapies for mesothelioma patients, including the Cancer Research UK-supported CONFIRM trial that was launched this year.

Alongside immunotherapy, researchers are looking at other ways to exploit mesothelioma biology to develop new, more targeted treatments, such as homing in on genes that are faulty in the disease or cutting off the tumour’s blood supply.

“Many things we already know about the disease could lead to fascinating treatments,” adds Fennell.

“Clinical trials are moving so quick that we’re learning a lot about basic science from patients, which is exciting.”

The battle is far from won

Mesothelioma may not be a common cancer, but that doesn’t mean it deserves a lack of attention. The disease can take decades to develop after asbestos exposure, which is why rates of people affected by the disease in the UK have snowballed since the 1990s, rising by 71% in the UK. But thankfully the snowball seems to be losing momentum and we’re expected to reach a peak within the next year or so, after which rates are predicted to start to tumble in the right direction.

But there is a worry that the downward trend may take longer than expected. “There’s still an dreadful lot of asbestos out there in ancient public buildings,” says Fennell, meaning there are still opportunities for exposure during building work. There’s also concern that some people may be unwittingly exposing themselves to lingering asbestos in their homes through DIY activities, which can release the fibres from within building materials.

While the dangers of asbestos have been fully embraced in the UK and other developed countries, the same cannot be said for other parts of the world.

Its production and use is still a huge problem in many countries, with the vast majority being exported from just 4 countries: Russia, China, Brazil and Kazakhstan. Around 80% of the world’s population live in countries where asbestos hasn’t been banned. It’s also in developing nations where asbestos continues to be used, a ticking time bomb for a future avoidable situation mirroring what was experienced in the UK.

The burden of mesothelioma could therefore shift from developed nations who have recognised this perilous dust as a major health threat, to countries that are rapidly expanding and consequently ploughing the material into much-needed infrastructure.

“The situation in Europe and other developed countries should act as a warning, but whether this will be heeded by countries still importing asbestos remains to be seen,” says Fennell.

What next?

With a lack of effective treatments for mesothelioma and a staggering 2,000,000 tons of asbestos still being produced each year, this global issue won’t be solved overnight. Greater awareness of the risks posed by exposure to asbestos, government action to replace its use with safe alternatives, better disease surveillance and monitoring, and more research and trials are all crucial steps needed to drive down the burden of mesothelioma worldwide.

And while there’s no doubt that asbestos causes mesothelioma, there are still many unanswered questions.

And while there’s no doubt that asbestos causes mesothelioma, Fennell points out there are still many unanswered questions.

“We still don’t know how much asbestos exposure is required to cause disease,” he says, “and we don’t have a clear understanding of how it causes mesothelioma.”

That’s why he’s collaborating with members of the Cancer Research UK-funded TRACERx lung cancer study, to start to probe the mesothelioma’s evolution and better know its underlying genetics.

“It’s early work, but it’ll allow us to interrogate mesothelioma in a way that hasn’t been done before to identify new drug targets,” he adds.

With much still to be learned, it’s this meticulous approach to mapping the biology of mesothelioma that will improve the outlook for the disease.

Justine

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