Restraint and release in tumour initiation: studying air pollutants and EGFR mutant lung cancer

Speaker Dr William Hill, Postdoctoral Training Fellow, Swanton Lab, Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute

Title Restraint and release in tumour initiation: studying air pollutants and EGFR mutant lung cancer

Host Jody Rosenblatt

 

Abstract A complete understanding of how environmental exposures promote cancer formation is lacking. Over 70 years ago, tumour formation was proposed to occur in a two-step process: an initiating step which induces mutations in normal cells, followed by a promoter step which triggers cancer development. We hypothesised that environmental particulate matter measuring <2.5μm (PM2.5), known to be associated with lung cancer risk, promotes EGFR mutant lung cancer by acting on cells harbouring pre-existing oncogenic mutations in normal lung tissue. We combine epidemiological evidence, functional pre-clinical mouse models and ultra-deep sequencing of normal tissue from clinical cohorts to decipher potential mechanisms of air pollutant induced tumour promotion. We propose that PM2.5 can trigger the expansion of pre-existing mutant lung cells via an inflammatory axis and this mechanism may be applicable to a range of cancer risk factors.