New blood test could be ‘holy grail’ of lung cancer prevention

A new blood-based molecular signature is capable of predicting lung cancer risk years before clinical diagnosis.

Lung cancer remains a major public health burden, with around a quarter of the estimated 15,000 Australians diagnosed annually reporting no history of smoking. Despite this, current screening programs remain narrowly targeted to individuals aged 50-70 who are current or former smokers, leaving a substantial at-risk population outside existing early-detection pathways.

Australian and UK-based researchers applied machine learning techniques to blood plasma protein datasets drawn from more than 48,000 participants, integrating matched cancer registry data to track individuals who later developed lung cancer.

When combined with established risk factors including age, smoking status, and prior lung disease history, the algorithm identified a panel of 14 blood proteins capable of predicting a future lung cancer diagnosis within five years. The researchers then validated this protein signature across eight international datasets, consistently finding elevated levels among individuals who later developed lung cancer, including a cohort with no smoking history.

“Figuring out who is at risk of developing cancer is the holy grail of cancer prevention medicine,” said Dr Clare Weeden, Laboratory Head in the Personalised Oncology Division at the Walter and Eliza Hall Institute of Medical Research (WEHI). “These findings bring us closer to a future where early intervention is possible, even before the cancer has a chance to develop.”

Further analysis indicated that the signature does not originate from tumour tissue itself. Instead, it appears to reflect an altered inflammatory environment in the lungs that precedes cancer development. Notably, elevated levels were also observed in individuals who later developed idiopathic pulmonary fibrosis or chronic obstructive pulmonary disease (COPD), suggesting the marker may represent a broader pre-disease inflammatory state shared across multiple lung conditions.

Charlie Swanton, Clinical Research Director and Principal Group Leader at the Crick, Professor in Cancer at University College London (UCL) and lead investigator for TRACERx, said “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. 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.”

The study also found that elements of the 14-protein plasma signature were elevated in association with IL-1β activity linked to air pollution exposure, raising the possibility that anti–IL-1β therapies could play a role in prevention for individuals exhibiting this inflammatory profile.

In 2017, the CANTOS trial led by Novartis evaluated the IL-1β inhibitor Ilaris (canakinumab) for cardiovascular disease prevention and reported, as an exploratory finding, a reduction in lung cancer incidence. However, the effect was modest at the population level, limiting its applicability as a broad preventive strategy in unselected groups.

Reanalysis of data from over 4,600 participants in the CANTOS study showed a more targeted effect. Individuals with a high baseline 14-protein signature experienced a marked benefit from Ilaris, with their lung cancer risk reduced by almost half. Within this subgroup, the number needed to treat to prevent one case of lung cancer was 55, comparable to established cardiovascular prevention approaches such as statin therapy.

By identifying individuals with this 14-protein inflammatory signature prior to lung cancer diagnosis, researchers suggest risk could be stratified more precisely, heralding a future for precision cancer prevention.

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