Abstract

Tumor-targeting bacteria elicit anticancer effects by infiltrating hypoxic regions, releasing toxic agents and inducing immune responses. Although current research has largely focused on the influence of chemical and immunological aspects on the mechanisms of bacterial therapy, the impact of physical effects is still elusive. Here, we propose a mathematical model for the anti-tumor activity of bacteria in avascular tumors that takes into account the relevant chemo-mechanical effects. We consider a time-dependent administration of bacteria and analyze the impact of bacterial chemotaxis and killing rate. We show that active bacterial migration toward tumor hypoxic regions provides optimal infiltration and that high killing rates combined with high chemotactic values provide the smallest tumor volumes at the end of the treatment. We highlight the emergence of steady states in which a small population of bacteria is able to constrain tumor growth. Finally, we show that bacteria treatment works best in the case of tumors with high cellular proliferation and low oxygen consumption.

Highlights

  • Cancers display huge variability between different patients and even in the same patient

  • We describe the tumor as being composed of three main constituents: tumor cells (TCs), bacteria and extracellular material

  • We proposed a mathematical model to study the influence of bacteria treatment on avascular tumor growth

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Summary

Introduction

Cancers display huge variability between different patients and even in the same patient. Low nutrient levels can lead to cell quiescence, a situation in which tumor cells delay metabolic activities and become less sensitive to standard chemotherapies (Challapalli et al, 2017) Such hypo-perfused areas are generally associated with poor patient outcome but, on the other hand, could be exploited for tumor targeting (Wilson and Hay, 2011). The use of bacteria for cancer therapy dates back hundreds of years, with doctors reporting tumor regression in several patients (Kramer et al, 2018) Such treatments caused some fatalities and the limited understanding of the therapeutic mechanisms of action shifted research efforts toward other strategies - especially radiotherapy (Kramer et al, 2018).

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