Air pollution may trigger lung cancer in never-smokers

A new mechanism has been identified through which very small pollutant particles in the air may trigger lung cancer in people who have never smoked, paving the way to new prevention approaches and development of therapies, according to late-breaking data [to be] reported at the ESMO Congress 2022.

In the laboratory studies, the Francis Crick Institute scientists showed that the same pollutant particles (PM2.5) promoted rapid changes in airway cells which had mutations in EGFR and in another gene linked to lung cancer called KRAS, driving them towards a cancer stem cell like state.

They also found that air pollution drives the influx of macrophages which release the inflammatory mediator, interleukin-1β, driving the expansion of cells with the EGFR mutations in response to exposure to PM2.5, and that blockade of interleukin-1β inhibited lung cancer initiation. These findings were consistent with data from a previous large clinical trial showing a dose dependent reduction in lung cancer incidence when people were treated with the anti-IL1β antibody, canakinumab.

In a final series of experiments, the Francis Crick team used state-of-the-art, ultradeep mutational profiling of small samples of normal lung tissue and found EGFR and KRAS driver mutations in 18% and 33% of normal lung samples, respectively.

"This research is intriguing and exciting as it means that we can ask whether, in the future, it will be possible to use lung scans to look for pre-cancerous lesions in the lungs and try to reverse them with medicines such as interleukin-1β inhibitors.,"one of the researchers said.

Ref:

Charles Swanton et al, Journal, Annals of Oncology