Restraint and release in tumour initiation: studying air pollutants and lung cancer Dr William Will (The Francis Crick Institute) presents his work on developing novel evolutionary animal models of lung cancer that better mimic what is observed in the clinic. Hosted by Dr Bill Grey.

Event details

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 which may be targetable for molecular cancer prevention.

About the speaker

Dr William Hill

William is a Postdoctoral Fellow in the Swanton lab, Cancer Evolution and Genome Instability Laboratory. William was awarded his PhD from Cardiff University for his work on cell competition at the earliest stages of pancreatic cancer. He demonstrated that KrasG12D mutant cells are selectively eliminated by normal neighbours from the adult pancreas in vivo. Loss of EphA2 was sufficient for retention of mutant cells and trigger early disease onset. William joined the group of Professor Charles Swanton in Autumn 2019. He is developing novel evolutionary animal models of lung cancer that better mimic what is observed in the clinic. This will improve our understanding of tumour evolution trajectories and intratumour heterogeneity.