A mathematical model for pancreatic cancer during intraepithelial neoplasia

Abstract

Cancer is the result of complex interactions of intrinsic and extrinsic cell processes, which promote sustained proliferation, resistance to apoptosis, reprogramming and reorganization. To understand the evolution of any type of cancer it is necessary to understand the role of the microenvironmental conditions and the impact of some molecular complexes and mechanisms on certain signalling pathways. As in most cancer quantitative models, the understanding of the early onset of cancer requires a multiscale analysis of the cellular microenvironment. In this paper we analyse a 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 the 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 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 to develop anti-inflammatory strategies that limit the emergence of more aggressive adenocarcinomas.