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This entry is part 10 of 10 in the series Grand Challenge

Giving scientists the freedom to think outside the box is important. But it also raises an interesting challenge around how to prioritise big ideas.

On the one hand, voyaging into the unknown to study the fundamentals of biology can yield unimaginable results. And giving scientists free rein to explore ideas has been at the heart of much scientific progress.

But other forms of research – for example, the meticulous and methodical design of clinical trials, or systematic analysis of ‘big data’, are also vital in helping develop the latest cancer treatments.

As an organisation that funds research on almost every aspect of cancer, balancing where the money goes across these different areas of research is no mean feat.

And it’s one reason why we divide our research focuses up into different areas – with each of our many funding schemes carefully managed and assessed.

But just over a year ago, we announced plans to do something completely new: the Cancer Research UK Grand Challenge.

It’s a £100 million scheme spanning the next five years that aims to tackle the biggest questions in cancer prevention, diagnosis and treatment. And it makes it all the more important to align the ‘hottest’ ideas with those that have the greatest potential impact.

It’s clearly caught the imagination of the global research community: in the five months since we opened the scheme 57 teams, comprising scientists from 25 different countries, have made an initial application for funding – proposing a whole host of possible ways to answer the questions.

And now, our expert panel has picked nine of them to go through to the next stage. Over the next few months they’ll hone these initial ideas, before a final decision is made on who will get the money.

And as we’ll explore below, these nine teams have already produced some potentially revolutionary new ideas.

A vaccine to prevent cancer

Vaccine_hero

One of our Grand Challenges was to develop a vaccine to prevent cancers developing – and one team has proposed a potentially ingenious way to solve it. Growing tumours crave a nourishing blood supply carrying nutrients and oxygen. The team proposes to develop a vaccine that could cut this supply line off

Professor Roy Bicknell, from the University of Birmingham, and his team of of experts from five countries, has already identified molecules that encourage blood vessels to grow. And these are also found at high levels within certain tumours, where they may be among the first signals that cause tumour blood vessels to form.

The team is proposing to develop a vaccine that would alert the immune system if the body begins to make these molecules, and thus prevent cancer cells from calling out for a new blood supply. If they can work out how to target the right molecules in the right healthy people, the vaccine could cut off a tumour’s life support before it has chance to start growing.

Taking down a virus

VaccineMapHero

Could a vaccine help wipe out cancers caused by EBV? Credit: Flickr/CC BY-NC-SA 2.0

Vaccines also featured as part of the second shortlisted application, aiming to tackle our second Grand Challenge: to eradicate cancers caused by the Epstein-Barr Virus (EBV).

Professor Alan Rickinson, from the University of Birmingham, has drawn together some of the world’s leading experts in EBV research from eight different countries. And they are proposing a two-pronged attack on the virus, which causes around 200,000 cases of cancer around the world each year.

Building on previous lab research, the first line of attack is to develop new treatments for cancers caused by the virus, and test these in clinical trials. The second, simultaneous, route of attack would involve studying in unprecedented detail how the virus affects molecules and processes inside infected cells.

They hope that pooling all the information learnt from these studies, and combining it with work to understand exactly how the immune system recognises EBV infection, will ultimately lead to a vaccine to prevent cancers caused by the virus, bringing with it the potential to prevent hundreds of thousands of cancer deaths.

What causes cancer?

Knowing how to prevent cancer relies heavily on understanding the processes that trigger it.

And researchers now know that these processes – whether environmental, lifestyle-based or genetic – leave a telltale pattern of damage within a cell’s DNA. Researchers have so far pinpointed 30 of these ‘mutational signatures’ in human tumours, but only half are linked to a known cause.

The third shortlisted team, led by Professor Mike Stratton from the UK’s Wellcome Trust Sanger Institute, including experts from three countries, aims to solve our third Grand Challenge – preventing cancers by pinpointing their causes.

During the shortlisting, one of the members of our Grand Challenge scientific panel – Professor Tyler Jacks, director of the Koch Institute in the US – described this approach as “grand in that it approaches many different types of cancer”. And Stratton’s team hopes they will be able to link more of these signatures to the processes that cause them.

They then plan to apply this to how the rates of different types of cancer vary around the world, piecing together where the impact of different causes is felt most.

The overall goal of this research would be to find ways of monitoring the appearance of these signatures in healthy people, thus opening up new ways to prevent the disease.

Better diagnosis

Eggs

Spot the difference. Credit: Flickr/CC BY-NC 2.0

Finding a way for doctors to spot the difference between potentially lethal tumours that need treating, and those that won’t cause a patient any harm, isn’t easy. But it’s the goal of our fourth challenge. And our panel shortlisted three teams hoping to take this on, all with a slightly different approach, and each focusing on a different type of cancer.

Led by the University of Oxford’s Professor Freddie Hamdy, and including researchers from three different countries, one team plans to focus on prostate cancer, throwing the latest DNA analysis and imaging technologies at thousands of tumour samples. They hope to find a unique ‘signature’ for both lethal and non-lethal tumours hidden in these data, which they then plan to test in a large clinical trial.

The next shortlisted team, led by the University of Southampton’s Dr Surinder Sahota, including experts from four different countries, is searching for a way to accurately predict whether patients with a pre-cancerous condition called monoclonal gammopathy of undetermined significance (MGUS) will go on to develop multiple myeloma, a cancer that starts in the bone marrow.

The team proposes to scour the DNA of people with MGUS in search of changes that are also found in myeloma. Combining this with information about faulty molecules inside cells and how the immune system reacts to myeloma, the team hopes to be able to predict, as early as possible, who will develop cancer.

The third shortlisted application for this challenge came from an international team led by Netherlands Cancer Institute’s Dr Jelle Wesseling. And according to another of our panel members, 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), it gets at a “critical clinical question” – working out a way of predicting whether cells that have started to become cancerous in the breast – so called ductal carcinoma in situ (DCIS) – will go on to become invasive breast cancer.

DCIS poses a real problem for doctors. It’s not yet possible to predict which patients will go on to develop dangerous breast cancers that need treatment, and which won’t.

By studying large collections of data from clinical trials in the UK, Europe and US, Wesseling’s team aims to solve this crucial problem, giving doctors an urgently-needed way of telling the difference between these cancers.

Virtual reality

Three applications were shortlisted to solve our Challenge of developing a ‘Google Street View’ for cancer. Solving this, said panel member Professor Suzanne Cory, from the Molecular Genetics of Cancer Division at The Walter and Eliza Hall Institute in Australia, could “move us into a different future”.

And with virtual reality in the mix it’s easy to see why.

The first team, led by Cambridge’s Professor Greg Hannon, and including scientists from five different countries, plans to focus on breast cancer. Combining technology that can track the movement and fate of cells in living tissue with molecular and genetic information, the team hopes to build a virtual reality experience that will allow researchers to ‘walk around’ inside 3D virtual tumours.

Breast cancers can be categorised into 10 distinct ‘types’ and the team plans to map each of these different diseases, along with clinical information about how patients with each type fared. This could open up an entirely new way for scientists and doctors to view how tumours develop and respond to treatment.

The second shortlisted application in this area is led by Professor Ehud Shapiro, from the Weizmann Institute in Israel, and once again featured an exciting proposal involving virtual reality.

Not content with mapping tumours in three dimensions, Shapiro’s team, made up of scientists from three different countries, plans to add a fourth: time.

Using the latest technology, they hope to track patients from diagnosis through treatment and even, in some cases, after death. In their application the team said that trying to look at the huge volumes of data that might result wouldn’t be “directly comprehensible”. So they’ll need to develop cutting edge new software to turn this complex data into a new, virtual reality.

Ultimately, they hope to produce the most comprehensive view of a tumour, stretching from its earliest origins to when it begins to spread and beyond. And they want to do this for every patient, with the hope of finding the best way to treat people in the future.

The third team, led by Dr Josephine Bunch from the National Physical Laboratory, propose combining three cutting-edge areas of research – machinery called mass spectrometry that can measure all the molecules inside individual cancer cells; the latest imaging technology; and next-generation genetic analysis – to generate detailed ‘molecular maps’ of tumours.

Combining the team’s expertise from several different scientific disciplines, they hope these maps will offer ways to group patients to help test personalised treatments, as well as finding new ways to accurately diagnose and monitor tumours.

What happens next?

We’ll now be supporting each team to further develop their approach, and submit a full application. Our expert panel will then meet again later this year to decide where the money will go.

On the subject of where this decision may end up, Professor Nic Jones, director of the Manchester Cancer Research Centre and member of our Grand Challenge scientific panel was quite clear during the shortlisting: “There’s no point doing exciting science if it’s not going to be transformational.”

And it would seem that, among these proposals, there are the teams and the ideas that have the potential to do both.

Nick