Secrets of the ‘super-avoiders’ – why do some people just not get cancer?
Not all people at high risk of developing cancer ever do, but we don’t know much about why. Now, a team of researchers is seeking to understand this in the hope that it could revolutionise prevention and treatment
Nearly one in two people will get cancer in their lifetime – yet many at high risk never develop the disease. Understanding why could unlock entirely new ways to prevent cancer – an idea explored in a special new episode of Goalhanger’s The Rest is Science podcast, a collaboration with Cancer Research UK that looks at the groundbreaking discoveries scientists are using to beat cancer at the game of evolution – shaping the future of medicine.
Until now, scientists have tended to focus less on obstacles to cancer development and more on identifying its causes, such as ageing – which gives genetic mutations time to build up in our cells. But some people consistently defy the odds; these “super-avoiders” somehow dodge cancer despite being at high risk, for example if they smoke or drink alcohol, are very elderly or have genetic variants linked to cancer.
We don’t yet know why certain individuals fit this “super-avoider” profile – so people can’t find out in advance if it applies to them.
Set up to investigate this is Team ATLAS, one of five interdisciplinary groups awarded $25m (£20m) each in early March by Cancer Grand Challenges. The researchers, from France, Denmark, Sweden, Switzerland, the UK and US, believe they can unlock some of the secrets in the immune systems of super-avoiders – potentially leading to new ways to prevent cancer, detect it earlier and improve therapies.
Unlocking the secrets that link Covid-19 and cancer
Team ATLAS is led by French paediatric immunologist Dr Paul Bastard, of the Imagine Institute, University of Paris Cité. He was inspired to investigate super-avoiders after studying the causes of severe Covid-19.
In March 2020, Bastard could be seen cycling between hospitals on his blue bicycle through the deserted streets of Paris during lockdown. He had special permission to collect blood samples to study why Covid-19 can result in no symptoms for some, while quickly killing others.
Bastard and his colleague Prof Jean-Laurent Casanova found that 10-15% of people with life-threatening Covid-19 had specific autoantibodies in their blood that undermined the immune system’s defences against the disease. Their team went on to show that these autoantibodies were present before people were infected with the coronavirus, while they were absent in people without symptoms or with mild Covid-19.
Bastard’s findings about the causes of severe Covid-19 led him to wonder whether autoantibodies might also play important roles in cancer. “We know cancers can be treated with immunotherapies, and that some autoantibodies can weaken the immune system,” he says. “Our hypothesis is that some autoantibodies could be cancer-inducing while others could be protective.”
Team ATLAS is assembling a global map of all the antibodies in the blood of more than 60,000 individuals, alongside their genetic profiles and records of other proteins found in their blood.
This cancer antibody “atlas” comprises data from individuals in various high-risk categories. Their antibody profile will be analysed and compared with people who developed cancer. The research could reshape our understanding of the immune system’s role in cancer, and deliver new ways to detect and treat the disease.
“Antibodies that contribute to cancer avoidance could be given to cancer patients or those at high risk of cancer, and those that lead to cancer could be removed from patients or those who do not have it yet,” says Bastard. “And if we find antibodies associated with the later occurrence of cancer, we could have a simple test that could prevent or detect cancer earlier.”
Bastard stresses that, while he believes autoantibodies could increase or reduce cancer risks, individuals can still improve their chances of avoiding cancer by, for example, stopping smoking, reducing alcohol intake and enjoying the sun safely.
Learning the secrets of animal super-avoiders
Not all super-avoiders are human. Scientists have identified some animals that have evolved strategies to keep cancer at bay. They hope that learning their tricks could lead to a better understanding of the causes of the disease in humans, as well as improved treatments and prevention strategies.
Cancer risk should increase with an organism’s size and age, but this isn’t always the case. This observation – called Peto’s paradox – was first made by epidemiologist Richard Peto in the 1970s. Bowhead whales, for example, rarely get cancer, despite sometimes growing to more than 19 metres in length and living beyond 200 years. And naked mole rats, while only 10-20 centimetres long, seem almost immune to cancer.
In 2022, evolutionary biologist Dr Alex Cagan, of the University of Cambridge and the Cancer Research UK Cambridge Centre, showed that genetic mutations accumulate more slowly in longer-lived animal species.
Cagan hopes that useful lessons can be learned by tracking what happens in cancer-avoiding animals when cancer-causing genetic mutations occur.
“Evolution has essentially been running cancer prevention trials for millions of years in different species,” he says. “If we can figure out the mechanisms that species are using, we can think about whether there are ways to mimic those mechanisms with therapeutics and lifestyle interventions.”
Unearthing the secrets of super-avoiders could open entirely new paths in the fight against cancer.