A blood test years before lung cancer: 14 proteins signal risk and flag who may benefit from prevention

A simple blood test could one day identify people at high risk of developing lung cancer—years before any tumor appears—and help select those most likely to benefit from an anti-inflammatory prevention therapy. Scientists report today in Cell that a 14-protein plasma signature predicts future lung cancer diagnosis more than five years in advance and, in a retrospective analysis of a large clinical trial, singled out individuals who gained protection from the drug canakinumab.

The work, led by senior author Charles Swanton at the Francis Crick Institute and University College London, with Tej Pandya as first author, used machine learning on UK Biobank proteomic data from nearly 50,000 people. The algorithm identified a 14-protein combination that, together with age, smoking history, and a past diagnosis of COPD, outperformed standard lung cancer risk models. The signature was validated in eight independent cohorts spanning the UK, US, Iceland, and China, along with a separate trial in Taiwan, comprising more than 2,000 incident lung cancer cases. Proteins in the signature are linked to inflammation, tissue remodeling, and lung surfactant production, and their levels were found to be elevated in future cancer patients more than five years before diagnosis.

Crucially, the signature does not simply reflect established tumors. It remained elevated in pre‑invasive lesions and did not drop after surgical removal of early cancers, suggesting it captures a cancer‑promoting state in the lung microenvironment. Using mouse models of EGFR-driven lung adenocarcinoma, the team showed that the signature’s components are expressed by normal lung cells—particularly alveolar and immune cells—and are induced by particulate matter (air pollution) or by the inflammatory signal interleukin‑1β (IL‑1β). Pollution exposure accelerated the emergence of so‑called KACs (keratin 8⁺/claudin 4⁺ alveolar transitional cells), which are intermediate cells that can seed tumours. Blocking IL‑1β reduced KAC expansion and early tumor formation in the mice.

The clinical relevance came from revisiting the CANTOS trial, a large cardiovascular study that had previously found that the anti‑IL‑1β antibody canakinumab unexpectedly lowered lung cancer incidence. In a retrospective analysis of 4,651 CANTOS participants, those with a high baseline 14‑protein signature had more than double the risk of later developing lung cancer. Among this high‑signature group, canakinumab cut lung cancer incidence by nearly half (from 3.88% on placebo to 2.06%), lowering the number needed to treat to 55—comparable to established cardiovascular prevention strategies. No benefit was seen in people with low signature levels.

The authors caution that the analysis is retrospective and hypothesis‑generating; prospective trials are needed to validate using the signature to guide therapy. The signature also performed less robustly in never‑smokers, a population where lung cancer is increasingly common. Still, the findings offer a path toward molecular cancer prevention: a blood test to identify people whose lungs show early signs of a tumour‑promoting inflammatory state, and a targeted drug to interrupt that process before malignancy takes hold.

Reference: Pandya T, Zagorulya M, Leung MM, et al. Plasma signals of lung tumor promotion for molecular cancer prevention. Cell. 2026. DOI: 10.1016/j.cell.2026.05.005