Stochasticity and Drug Effects in Dynamical Model for Cancer Stem Cells

Cancers (Basel). 2023 Jan 21;15(3):677. doi: 10.3390/cancers15030677.

Abstract

The Cancer Stem Model allows for a dynamical description of cancer colonies which accounts for the existence of different families of cells, namely stem cells, highly proliferating and quasi-immortal, and differentiated cells, both undergoing cellular processes under numerous activated pathways. In the present work, we investigate a dynamical model numerically, as a system of coupled differential equations, and include a plasticity mechanism, of differentiated cells turning into a stem state if the stem concentration drops low. We are particularly interested in the stability of the model once we introduce stochastically evolving parameters, associated with environmental and cellular intrinsic variabilities, as well as the response of the model after introducing a drug therapy. As long as we stay within the characteristic time scale of the system, defined on the base of the needed time for the trajectories to converge on stable states, we observe that the system remains stable for the main parameters evolving stochastically according to white noise. As for the drug treatments, we discuss a model both for the kinetics and the dynamics of the substance in the organism, and then consider the impact of different types of therapies in a few particular examples, outlining some interesting mechanisms, such as the tumor growth paradox, that possibly impact the outcome of therapy significantly.

Keywords: activator; cancer stem cells; cytotoxic and cystostatic drugs; inhibitor; plasticity; stochasticity; tumor heterogeneity; ultrasounds.

Grants and funding

The research was funded in part by ITMO Cancer of Aviesan within the framework of the 2021–2030 Cancer Control Strategy, on funds administrated by Inserm (PCSI 2021, MCMP 2022 and by Agence Nationale de la Recherche under the contract EpiMorph (ANR-2018-CE13-0008).