A phenotype-structured mathematical model for the influence of hypoxia on oncolytic virotherapy

TL;DR

This paper presents a new mathematical model that explores how hypoxia within tumors influences the effectiveness of oncolytic virotherapy, considering spatial, epigenetic, and evolutionary tumor heterogeneity.

Contribution

It introduces a novel continuous model integrating tumor heterogeneity and oxygen gradients to better understand virotherapy dynamics under hypoxic conditions.

Findings

Hypoxic tumor regions reduce viral replication effectiveness.

Oxygenation levels influence tumor cell susceptibility to viruses.

Model simulations suggest personalized virotherapy strategies based on tumor oxygenation.

Abstract

The effectiveness of oncolytic virotherapy is significantly affected by several elements of the tumour microenvironment, which reduce the ability of the virus to infect cancer cells. In this work, we focus on the influence of hypoxia on this therapy and develop a novel continuous mathematical model that considers both the spatial and epigenetic heterogeneity of the tumour. We investigate how oxygen gradients within tumours affect the spatial distribution and replication of both the tumour and oncolytic viruses, focusing on regions of severe hypoxia versus normoxic areas. Additionally, we analyse the evolutionary dynamics of tumour cells under hypoxic conditions and their influence on susceptibility to viral infection. Our findings show that the reduced metabolic activity of hypoxic cells may significantly impact the virotherapy effectiveness; the knowledge of the tumour's oxygenation could, therefore, suggest the most suitable type of virus to optimise the outcome. The combination of numerical simulations and theoretical results for the model equilibrium values allows us to elucidate the complex interplay between viruses, tumour evolution and oxygen dynamics, ultimately contributing to developing more effective and personalised cancer treatments.