Grand Challenge two: wipe out cancers caused by the Epstein-Barr Virus

In October 2015 we launched the Cancer Research UK Grand Challenge – a £100m scheme to tackle seven of the biggest challenges in understanding and treating cancer.

And in a series of posts over the next two months we’ll be exploring each of the seven Grand Challenge questions set by a panel of the world’s leading cancer experts. The second of our Grand Challenge topics is posing the question: can we wipe out cancers caused by the Epstein Barr Virus?

The Epstein-Barr Virus (EBV) is one of the most common viral infections in humans – around 19 in every 20 adults carry the virus. In terms of the sheer number of people infected, it’s one of the most prolific viruses the world has ever seen.

And in most of us, it appears to cause no harm at all.

But there’s a sinister side to the virus too. In some people, it can cause cancer.

In fact, EBV was the first virus found to cause cancer in humans. We now know that, every year, EBV infections trigger 200,000 new cases of cancer – and more than 140,000 deaths – worldwide.

These are mainly certain forms of lymphoma, as well as cancers that start at the back of the nose and throat (the nasopharynx), and some cases of stomach cancer.

Molecules produced by EBV can send infected cells into overdrive, telling them to keep dividing. But diet, genetics and exposure to other infections also play an important role in cancer developing.

This dark side to what’s a relatively common infection has been felt in some parts of the world more than others. China and parts of South East Asia have seen increasing rates of those cancers affecting the nasopharynx, while rates of EBV-linked lymphoma have hit certain parts of sub-Saharan Africa in particular.

And while expert teams dotted around the globe have chipped away at the challenge of tackling EBV-linked cancers, some believe the geographical spread of these cancers – hitting mainly the developing world – may have stifled interest in studying them.

Now that could be set to change.

EBV3

A defined and achievable goal

Professor Sir David Lane – Scientific Director of the Ludwig Institute for Cancer Research, Chief Scientist at Singapore’s Agency for Science, Technology and Research (A*STAR) and one of the members of our Grand Challenge Advisory Panel – believes that understanding the trigger behind these tumours actually gives us a real chance of tackling them.

These cancers have a known cause: a virus. And we have a long and successful history of dealing with viruses – Professor Sir David Lane

“One of the exciting things about this challenge is that it has a very defined – and in my opinion achievable – goal,” he explains.

“These cancers have a known cause: a virus. And we have a long and successful history of dealing with viruses – either preventing people being infected using vaccines, or successfully treating infections.

“There’s no reason we can’t do the same with EBV.”

Lane sees the attempt to stop people becoming infected in the first place, for example through vaccination, as a key focus for this challenge.

“There’s a precedent with the success story of vaccines against the human papillomavirus (HPV), which causes several types of cancer, notably cervical cancers,” he says.

HPV vaccines began their development in the early 1990s and were rolled out as part of a national programme to immunise schoolgirls in the UK in 2008. The vaccination programme is predicted to save thousands of lives in the future.

And finding a similar way to prevent EBV infection could stop cancers caused by the virus developing, and save lives.

But for Lane, there are potentially even bigger benefits ahead – and it’s not just about vaccines.

“There are definitely some cancers we know are caused by EBV. But science is an ever-moving field, and there may be other cancers linked to the virus we don’t know about yet.”

“One theory is that fighting the infection could exhaust or dampen down our immune response, which might help other types of cancer escape immune destruction,” says Lane.

“The important point is that the solution isn’t necessarily a vaccine. There may be ways of uncloaking the virus to immune cells, helping people get rid of the infection themselves rather than having low level infection for years – sometimes their whole lives.”

‘It’s not been lack of ideas that’s held us back’

Research into EBV-linked cancers has been ongoing for 50 years. And there are a lot of scientists with in depth knowledge of the virus.

But Lane believes that up until now, it’s lacked the momentum that’s needed to turn research into new ways to tackle the disease.

The Grand Challenge would be a significant boost to the efforts of the vaccine research community

– Professor Alan Rickinson

“We’ve had a patchwork of researchers dotted about the world, but no real large, united front to tackle this head on,” he says.

“And this is where the Grand Challenge could really turn the tables.”

One of the scientists leading the charge is Professor Alan Rickinson, a Cancer Research UK-funded world leader in EBV research.

He believes that some of the reasons why an EBV vaccine hasn’t progressed as far as it could have are a lack of political will and limited backing from the pharmaceutical industry.

“It’s not been lack of ideas that’s held us back,” he says. “We’ve long had the goal of developing a vaccine to protect people from becoming infected with the virus. And the success of the HPV vaccine is a shining example of what science can achieve.”

But viruses are very different from one another, and the development of the HPV vaccine doesn’t automatically mean it will be simple to make an effective EBV vaccine too.

That’s because EBV is very different from HPV. EBV is a type of virus called a ‘herpesvirus’, and at the moment, there are no protective vaccines against any human herpesviruses.

“An EBV jab would be a first,” says Rickinson, “and a very important first!”

“The Grand Challenge would be a significant boost to the efforts of the vaccine research community.”

EBVmap

Beyond the vaccine

But while a vaccine would be a big step forwards, there’s also an urgent need for better treatments for the 200,000 patients diagnosed every year with EBV-linked cancers.

Dr Emma King, a leading head and neck surgeon at the University of Southampton, is carrying out clinical trials testing new ways to boost the immune response against cancers, many of which are caused by the HPV virus.

“A huge number of cancer cases worldwide are caused by viruses,” she explains. “And one of the big questions we still need to answer is why some people’s immune systems recognise and get rid of viruses, while other people can’t clear the infection and are at risk of developing cancer.”

According to King there are several key factors that might play a role – the virus, other infections the immune system has to cope with, lifestyle factors, and of course our genetics.

She believes that curing these cancers will need a multi-pronged attack, and this may differ between patients. For example, it could involve combining a vaccine with a drug that stops cancer cells hiding from immune cells, or combining radiotherapy with immune boosting drugs.

“Every step is a step in the right direction,” she says. “But science is expensive, and the Grand Challenge will help boost progress by bringing together experts from different fields, helping us learn from each other.”

The patient perspective

As a patient representative I’ve always struggled with the many acronyms within the projects I’ve been involved in. Going back and forth until they are fully ingested reminds me of when I was a youngster at school learning my lines for the school play. Reading question two of the Grand Challenge another acronym for a cause of cancer pops up – EBV- Epstein-Barr Virus. As with the first challenge, developing a vaccine could be the answer for preventing infection with EBV. But as with all of the Grand Challenge questions it’s more complex, requiring a change in the way research is usually done. Throughout the Grand Challenge workshops I could hear the positivity in the talks given by the scientific community, the freedom of expression used by the presenters was open and cavalier. A world apart from the safety that one might feel when your colleagues all understand the acronyms. ‘Imagine’ was a much used word, along with ‘Reach for the stars’ and ‘If we don’t try we’ll never succeed’. The cancer world is full of acronyms, an ABC of symptoms, causes, types, and treatments. There are no acronyms for cure. Taking on a challenge with this attitude and breaking out of the comfort zone of acronyms is exactly what’s needed to eradicate EBV-induced cancers from the world.

– Terry, patient panel member for the Grand Challenge

Research has revealed a lot about EBV – and other viruses linked to cancer – over the past 50 years, but the story is just beginning. The viruses themselves are only part of the picture; our genetics and environment also combine to play a role in cancer developing.

But with all the knowledge we have, curing, or preventing, EBV-linked cancers seems within reach – it just needs that investment to make it a reality. And the Grand Challenge could provide exactly that.

“The whole idea of a ‘Grand Challenge’ is tremendously exciting,” says Lane. “It’s a different way of doing research. It brings scientists across the world together and approaches these large problems by combining a wide breadth of skills, knowledge and technology.”

And with the potential of saving 140,000 lives a year across the world, it will certainly have a big impact.

Emma