Scientists from the Francis Crick Institute and University College London, supported by Cancer Research UK, have identified a new mechanism by which very small airborne particles of pollution may cause lung cancer in people who have never smoked, paving the way for the development of new preventative measures and therapeutics. These findings will be presented at the ESMO Congress 2022, where they will pave the way for the development of new prevention strategies and therapies. The particles, which are commonly present in vehicle exhaust and smoke from fossil fuels, are linked to the risk of non-small cell lung cancer (NSCLC) and are responsible for over 250,000 lung cancer deaths worldwide each year.
The new findings are based on clinical and laboratory research on mutations in the EGFR gene, which are seen in almost half of never-smokers with lung cancer. Exposure to rising amounts of airborne particulate matter (PM) 2.5 micrometres (m) in diameter was associated with an increased risk of non-small cell lung cancer (NSCLC) with EGFR mutations in a study involving almost half a million residents of England, South Korea, and Taiwan.
In laboratory investigations, scientists from the Francis Crick Institute demonstrated that the same pollution particles (PM2.5) stimulated rapid alterations in airway cells with mutations in the lung cancer-linked genes EGFR and KRAS, moving them towards a stem cell-like state. In addition, they discovered that air pollution stimulates the inflow of macrophages that release the inflammatory mediator interleukin-1, which drives the development of cells with EGFR mutations in response to exposure to PM2.5, and that blocking interleukin-1 decreased the onset of lung cancer. Canakinumab, an anti-IL1 antibody, was shown to reduce the incidence of lung cancer in a dose-dependent manner in a prior, major clinical trial.
In a final series of tests, the Francis Crick team identified EGFR and KRAS driver mutations in 18% and 33% of normal lung tissue samples, respectively, using ultradeep mutational profiling.
LBA1 ‘Mechanism of action and an actionable inflammatory axis for air pollution-induced non-small cell lung cancer in never smokers’ will be presented by Charles Swanton during Presidential Symposium 1 on Saturday, 10 September, 16:30 to 18:00 CEST in Paris Auditorium. Annals of Oncology, Volume 33 Supplement 7, September 2022. www.esmo.org/meetings/esmo-congress-2022