268P Modelling clonal dynamics for early lung squamous cell carcinoma prediction and interception

Airway basal cells are the cells of origin for lung squamous cell carcinoma (LUSC). Normally, they undergo neutral competition and maintain epithelial integrity through balanced self-renewal and differentiation. Carcinogen induced alterations disrupt this and confer fitness advantages that enable specific basal cell clones to outcompete neighbours and expand across the airway – a prerequisite for LUSC development. Defining these early events is critical for predicting and intercepting LUSC. TP53 loss is postulated to drive aberrant basal cell clonal expansion in vivo; however, these early dynamics have not been modelled in vitro.