What can cancer research learn from people who don't get cancer?

When drugs designed to put the brakes on cancer cells aren’t working, should we push the accelerator instead?

And is there an untapped power in our brains that could help us keep tumours in check?

Cancer isn’t a single disease, and nothing about it is simple, either. For all the progress we’ve made, there are still vital questions that haven’t been explored – questions no single researcher, institution or even country could take on alone. 

Today, Cancer Grand Challenges has awarded five pioneering international teams up to £20m each to seek out answers to five of those questions.

Read on to meet the teams and find out how Cancer Grand Challenges’ unique approach is helping them find entirely new ways to prevent, detect and treat cancer.

Introducing the new teams

Almost 1 in 2 people in the UK will be affected by cancer at some point in their life. If it’s not you, there’s a good chance it’s the person next to you – sometimes because of risk factors like lifestyle and genetics, but sometimes for reasons we can't explain. 

Team ATLAS is mapping out the way to an answer.

ATLAS plans to study the immune systems of people who live into their 100s, twins that do and don’t get cancer and people who smoke but stay cancer-free to see what sets ‘cancer avoiders’ apart. In particular, team members will be looking for distinctive “autoantibodies”, targeting proteins that can either empower the immune system to stop cancer before it starts, or hold it back until it’s too late.  

Over the same funding period, REWIRE-CAN will be looking at cancer treatment - just not from an angle anyone's used to. Instead of trying to block the growth of hard-to-treat bowel cancers with targeted drugs, the team will be finding out if it’s possible to hotwire the cells and press down their accelerators until they crash or self-destruct. 

Team ILLUMINE will also be reaching into our cells, but their tools are more like torches than screwdrivers. ILLUMINE's researchers are setting out to solve the mysteries of the ‘dark proteome’, a group of elusive proteins that might drive cancer. At the moment, we don't know what these proteins do, or when and how they're made. ILLUMINE's research will change that, and could help give us new ways to treat some types of cancer.

Meanwhile, the CAUSE team are setting out to solve similar mysteries hidden in the world around us. They’re going to combine new tools and innovative chemistry to uncover unknown causes of DNA damage, without which cancer couldn’t start at all.

Finally, InteroCANCEption will be turning their thoughts to the human brain itself. The team plans to use the incredible signalling powers that start in our heads to slow tumours down, lessen their symptoms and guide the immune system to target cancer cells more effectively. 

“Cancer is a deeply complex and constantly evolving set of challenges - each with profound consequences for people and families worldwide,” said Professor Charles Swanton, chair of the Cancer Grand Challenges Scientific Committee, which led the interview process for the new teams.  

“Addressing challenges of this scale demands bold, interdisciplinary science, and it is this approach that has the potential to fundamentally change how we understand and treat cancer.”

Collaboration and the CAUSEs of cancer 

We co-founded Cancer Grand Challenges with the National Cancer Institute in the US in 2020. Already, funded teams are transforming how we think about the causes of cancer and revealing powerful new ways we can treat it.

The five new teams, which span 34 institutions in nine countries, bring the Cancer Grand Challenges community to more than 1,800 researchers and collaborators, all focused on answering the toughest questions about the biggest health problem of our time. 

That community has been particularly important for team CAUSE, led by Professor Ludmil Alexandrov from the University of California San Diego.  

CAUSE plans to build on the groundbreaking work of team Mutographs, one of the very first research teams we supported with Cancer Grand Challenges funding. As part of Mutographs, Alexandrov helped show that it’s possible to understand the causes of cancer by looking for the marks, or mutational signatures, they leave on our DNA.  

Mutographs proved we can match mutational signatures to specific cancer-causing exposures and identified clues as to why the rates of some cancers differ so much around the world. Now, team CAUSE is bringing together chemists, geneticists and experts in DNA damage and repair to develop that insight into a practical way of preventing cancer.  

The team's work will trace exactly how a passing exposure to a ‘mutagen’ can leave a lasting mark on our DNA. Researchers will then use what they learn to identify the specific causes of unexplained mutational signatures linked to kidney, liver and bowel cancer. They'll also create tools other research groups can use to uncover new ways of preventing cancers all over the body. 

ILLUMINE and the funding partnerships helping light the way 

For this round, Cancer Grand Challenges has also received funding from the Bowelbabe Fund for Cancer Research UK, the Cancer Research Institute in the US, the Children Cancer Free Foundation (KiKa), the KWF Dutch Cancer Society, the Torrey Coast Foundation and Yosemite (an oncology-focused venture firm).  

ILLUMINE and REWIRE-CAN have both been supported by more than one of these partners, which underscores the growing importance of international collaboration and cooperation in cutting-edge cancer research. 

ILLUMINE will investigate the “dark” unexplained proteins operating in the shadowy corners of our cells, which could give us new ways to target hard-to-treat cancers.

The team is supported by the Cancer Research Institute and KiKa, two organisations that bring different perspectives to the project. 

"One of the unique features of Cancer Grand Challenges is the scale of funding, which lends itself towards collaboration on the scientific side and on the funder side,” said Alicia Zhou, CEO of the Cancer Research Institute. “This allows CRI to work alongside like-minded organisations to fund projects that would otherwise be too complex or too interconnected for traditional funding models.” 

Like-minded doesn’t mean identical. CRI targets its investments to improve immunotherapy, while KiKa, based in the Netherlands, is an important funder of research into cancers affecting children and young people. In the last Cancer Grand Challenges funding round in 2024, KiKa supported the KOODAC and PROTECT teams, both of which are developing new types of targeted drugs. ILLUMINE will build on that work by studying the role of dark proteins in brain tumours that affect children and young people.  

“By combining diverse expertise, sharing knowledge and resources, and fostering collaboration across borders, we move closer to highly necessary breakthroughs for children with cancer,” said Jakolien van Eijk, KiKa's managing director. “Achieving this requires both outstanding scientists and significant funding, and Cancer Grand Challenges brings these factors together.” 

On the immunotherapy side, Zhou highlights the potential for team ILLUMINE to discover proteins that could be used to create new cancer vaccines.  

“Truly, it feels like we are on the precipice of a paradigm-shifting breakthrough,” she said. “Team ILLUMINE’s work will allow the field a much deeper understanding of potential targets for cancer vaccine development.” 

ATLAS: From COVID-19 to Cancer Grand Challenges 

By focusing on outstanding challenges, rather than specific areas of study, Cancer Grand Challenges brings together boundary-crossing teams that other cancer research initiatives can’t. 

Dr Paul Bastard, the head of team ATLAS, took the long route into cancer research. His journey began in March 2020, on the bicycle he used to travel from hospital to hospital through the deserted streets of lockdown Paris. At each stop, he collected blood samples from patients with COVID-19. 

As the pandemic waxed and waned, Bastard’s study of those samples began to reveal the biology that made it such a complicated problem. His research showed that autoantibodies, proteins people carried long before they were infected with COVID-19, determined whether their immune system could protect them from the virus. 

Cancer and COVID-19 are about as different as two diseases can be. But the immune system has to defend us against them both. Now, Bastard and his colleagues are going to investigate whether autoantibodies are a missing link.

We sometimes talk about cancer cells “disguising” themselves from the immune system, but ATLAS believes that cancer can never go completely unnoticed. Autoantibodies are proteins that guide the immune system to target things that look like 'self', so they could play a crucial role in determining whether cancer cells are removed when they're spotted or allowed to grow.

In cancer avoiders, helpful autoantibodies may make it easier for the immune system to target potentially cancerous changes in 'self' cells. Other people may be vulnerable to cancer because they have autoantibodies that block some of the 'self' cells in the immune system, similar to the COVID patients Bastard set out to help back in 2020.

Though it stemmed from research into infectious diseases, ATLAS’s work has the potential to change our understanding of the immune system’s role in cancer. Ultimately, it could provide us with the tools to make more people cancer avoiders.

InteroCANCEption and the role of patient advocates 

Every single Cancer Grand Challenges team also includes patient representatives with direct experience of cancer. Their guidance keeps the research focused on making advances that save and improve lives.

Federica Valsecchi became a patient advocate after losing her mother to pancreatic cancer, one of the hardest types to detect early and treat successfully. Federica is now part of the InteroCANCEption team, which is investigating the role of interoception, the brain’s ability to monitor and control the body, in the way cancer develops.

The team's long-term goal is to develop ways of modulating the brain and nervous system to keep even hard-to-treat tumours like pancreatic cancer in check, as well as to support the immune system and lessen symptoms.

“By serving as an advocate for this global team, I can help make sure that as we map the complex ‘body-brain axis’, the research remains focused on the outcomes that matter most to patients, such as improving survival and quality of life,” said Federica.

“I want to help drive a shift from purely academic discovery to developing tangible therapies, ensuring that these novel "nerve-modifying" technologies are designed with the patient's daily reality and dignity at the forefront.” 

Federica is also the founder of Fondazione Nadia Valsecchi, which she named after her mother. Across Italy and the US, the foundation supports pancreatic cancer research and helps patients better understand their disease through clear communication and education. 

The rebellious spirit of REWIRE-CAN 

The Bowelbabe Fund for Cancer Research UK, set up to continue the legacy of Dame Deborah James, plays a very similar role to Federica’s foundation. As well as raising awareness of bowel cancer, it has already helped fund two Cancer Grand Challenges teams focused on understanding, preventing and treating the disease.

From today, the Bowelbabe Fund will also support team REWIRE-CAN, which is embarking on exactly the kind of brave, unconventional research project Dame Deborah believed in.

Cancer is defined by its tendency towards uncontrolled growth, so targeted drugs are usually designed to slow it down. REWIRE-CAN's researchers are turning that idea on its head. They're going to treat bowel cancer by speeding it up.

Controversial as it sounds, there's good science behind this approach. Recently, evidence has begun to suggest that cancer cells aren’t actually in constant overdrive. Instead, they survive and multiply because they’re able to maintain their own balanced ‘Goldilocks’ state. It's as if they've had the two cups of coffee they need to keep them energised, not the four or five that would tip them over into jitters and stress.

But this is much more extreme than extra caffeine. REWIRE-CAN plans to develop and rigorously test a new type of cancer treatment that hyperactivates bowel cancer cells, putting them under so much stress they self-destruct.

Resistance to current treatments is a growing problem in bowel cancer, particularly for people with advanced disease and for younger adults, who are being diagnosed at rising rates. The team will use patient samples and cutting-edge lab models to help them find a way past this problem. They also plan to exploit the same ‘rewiring’ approach to find ways of making bowel cancers that have begun to resist today's treatments vulnerable again. 

The breakthroughs and discoveries to come

You can find out more about ATLAS, CAUSE, ILLUMINE, InteroCANCEption and REWIRE-CAN in the latest edition of the Cancer Grand Challenges Discover magazine.  

Together, the new teams are poised to make transformative discoveries and use them to benefit the people who need them most. We’ll be sharing news on their progress here on Cancer News and via the Cancer Grand Challenges website. 

“Cancer continues to place an immense burden on people and health systems worldwide”, said Michelle Mitchell, our chief executive. “Meeting that challenge demands both speed and scale in how we do research. We must build on past breakthroughs and empower scientists to push beyond the limits of what’s been possible before. 

“Cancer Grand Challenges unites world‑leading teams to take on these extraordinary questions with the scale and freedom needed for true breakthroughs. We’re thrilled to see this new wave of innovators step forward, ready to redefine what’s possible for people affected by cancer.”