Scientists from the Francis Crick Institute and University College London (UCL) have identified a blood signature that indicates a risk of lung cancer years before a diagnosis. The findings could help to develop prevention strategies for this deadly disease.
The paper, published in Cell, suggests experts may soon be able to identify individuals who would benefit from preventative drugs pre diagnosis.
An Australian problem
According to the Cancer Council, lung cancer is among the top five most diagnosed cancers in Australia, with around 15,000 new cases each year.
Lung cancer occurs when abnormal cells grow and spread in the lungs. 85 percent of lung cancers begin in the outer parts of the lungs in larger airways, although extreme cases can begin in the middle and spread much more quickly.
Tobacco smoking is the biggest cause of lung cancer, however other factors such as exposure to air pollution are increasingly causing diagnoses in people who have never smoked. Now, around a quarter of Australians diagnosed with lung cancer have no history of smoking.
Despite these alarming new risks, lung cancer screening programs are strictly offered to those aged between 50-70 who currently smoke or have a history of smoking. This means many at-risk people have no access to early detection tools.
Catching illness early
As we age, all of us accumulate cells with cancer-causing mutations. Cancers rely on these mutations to grow, yet these mutated cells are not enough to trigger cancer without additional factors, such as the environment.
Setting out on their new project, the research team (who previously worked on a paper showing how air pollution can cause cancer) wanted to find a signature that could accurately predict the risk of lung cancer.
By using machine learning, they were able to cross-reference blood plasma protein data from over 48,000 UK Biobank participants to individuals on the cancer registry. Experts could then look for commonalities in the bloodwork of subjects who later developed cancer.
As well as age, smoking status and history of lung disease, the machine learning algorithm successfully identified 14 key proteins in blood that could predict a lung cancer diagnosis within the next five years.
The team then used these markers across eight international datasets, and found that all 14 proteins were more common in those with lung cancer. The signature was also common in people who went on to develop idiopathic pulmonary fibrosis or chronic obstructive pulmonary disease.
Evidence amongst those who develop other lung conditions suggests the signature may capture a shared, pre-disease state of lung inflammation.
“Finding a signal for an inflammatory state in the lungs has given us insight into this window of opportunity, when preventative treatment could work best,” says Clinical Research Director and Principal Group Leader at The Crick, and Professor of Cancer at UCL, Charlie Swanton.
“This work supports a relatively new idea in the field, that some common age-related diseases, causing a high burden of disease in the community, share a common, presymptomatic state of inflammation.
“We think the signature could in the future help to predict and help prevent lung cancer and other lung diseases.”
Hope for the future
The team’s earlier research found that air pollution can trigger immune cells in the lungs to release an inflammatory signal, which can wake up dormant cells with cancer mutations.
Exposure to pollution also increases the presence of those 14 signature proteins found to indicate future lung disease, and increases the population of KAC cells that normally respond to injury but can also become cancerous if mutations are present.
According to Dr Clare Weeden, a corresponding author on the paper, “what surprised us was that very different lung cell types all seemed to converge on the same intermediate state before becoming cancerous – suggesting KACs represent a common vulnerability in lung adenocarcinoma.
“If we can identify people in whom this process is active and intervene at that stage, we may be able to prevent cancer before it develops.”
Amazingly, the team were able to block the inflammatory signal in the lungs of mice exposed to pollution, which limited the number of KAC cells and slowed early tumour development. This suggests that, with the right drugs, lung cancer could be prevented in people whose lungs are showing this inflammatory signal.
“Figuring out who is at risk of developing cancer is the holy grail of cancer prevention medicine,” says Dr Weeden.
“This proof-of-concept study offers new ideas that could fill this critical knowledge gap.
“In doing so, these findings bring us closer to a future where early intervention is possible, even before the cancer has a chance to develop.”
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