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 their 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 qualitative 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.