Abstract 861: Modelling the role of EGFR mutation in the initiation of never-smoker lung cancer

Genetic mutations associated with never-smoker lung cancer frequently appear in normal lung tissue, in both cancer and non-cancer patients. It is unclear what circumstances are required for a mutation to fix in healthy tissue and eventually lead to a tumor. To investigate this, alveolar type-II murine cells were grown in a 3D nutrient system, forming spheroidal clusters. The volumes of these clusters were measured at 7 and 14 days and a mathematical model was devised to describe their growth. In the absence of an EGFR mutation, variations in growth between clusters can be explained by a skew-normal distribution of initial division rates. These rates decline exponentially as the clusters age, and the decline rate is the same across clusters. When cells possess an epidermal growth factor receptor (EGFR) mutation or are grown in the presence of interleukin-1 beta (il-1b) growth factor, clusters form more complex shapes, which we believe may be driven by branching processes and cell-cell interactions. Accordingly, more complex models are needed to explain their development. This work lays the groundwork for new, parameterized models of mutational spread in lung tissue, and a deeper understanding of the role of mutation in carcinogenesis. Citation Format: Helena M. Coggan, Clare E. Weeden, Mohit Dalwadi, Charles Swanton, Philip Pearce, Karen M. Page. Modelling the role of EGFR mutation in the initiation of never-smoker lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 861.