Cell death and life in cancer: mathematical modeling of cell fate decisions

TL;DR

This paper develops a discrete mathematical model to analyze how cancer cells decide between survival, apoptosis, and necrosis, providing insights into tumor development and potential therapeutic targets.

Contribution

It introduces a novel discrete modeling approach with sensitivity analysis to identify key parameters influencing cell fate decisions in cancer.

Findings

Identifies critical parameters affecting cell death choices.

Predicts cellular responses to death receptor engagement.

Discusses implications for cancer therapy strategies.

Abstract

Tumor development is characterized by a compromised balance between cell life and death decision mechanisms, which are tighly regulated in normal cells. Understanding this process provides insights for developing new treatments for fighting with cancer. We present a study of a mathematical model describing cellular choice between survival and two alternative cell death modalities: apoptosis and necrosis. The model is implemented in discrete modeling formalism and allows to predict probabilities of having a particular cellular phenotype in response to engagement of cell death receptors. Using an original parameter sensitivity analysis developed for discrete dynamic systems, we determine the critical parameters affecting cellular fate decision variables that appear to be critical in the cellular fate decision and discuss how they are exploited by existing cancer therapies.