A mathematical model for pancreatic cancer during intraepithelial neoplasia

Cancer is the result of complex interactions of intrinsic and extrinsic
cell processes, which promote sustained proliferation, resistance to
apoptosis, reprogramming, and reorganization. The evolution of any type of
cancer emerges from the role of the microenvironmental conditions and the
impact of some molecular complexes on certain signalling pathways. The
understanding of the early onset of cancer requires a multiscale analysis
of the cellular microenvironment. In this paper, we analyse a quantitative
multiscale model of pancreatic adenocarcinoma by modelling the cellular
microenvironment through elastic cell interactions and their intercellular
communication mechanisms, such as growth factors and cytokines. We focus
on the low-grade dysplasia (PanIN 1) and moderate dysplasia (PanIN 2)
stages of pancreatic adenocarcinoma. To this end, we propose a gene
regulatory network associated with the processes of proliferation and
apoptosis of pancreatic cells and its kinetics in terms of delayed
differential equations to mimic cell development. Likewise, we couple the
cell cycle with the spatial distribution of cells and the transport of
growth factors to show that the adenocarcinoma evolution is triggered by
inflammatory processes. We show that the oncogene RAS may be an important
target for developing anti-inflammatory strategies that limit the
emergence of more aggressive adenocarcinomas.