# Optimization of SOX2 Expression for Enhanced Glioblastoma Stem Cell Virotherapy

## TL;DR

This study uses a mathematical model to show how adjusting SOX2 levels can improve Zika virus treatment for brain cancer stem cells.

## Contribution

A novel ODE model reveals critical thresholds for SOX2 and viral replication to optimize Zika virotherapy for glioblastoma.

## Key findings

- Critical thresholds for SOX2 and viral replication were identified to change equilibrium stability.
- Transcritical and Hopf bifurcations were observed in population dynamics affecting therapeutic outcomes.
- Optimal SOX2 expression and viral bursting size enhance Zika virotherapy efficacy against glioblastoma stem cells.

## Abstract

The Zika virus has been shown to infect glioblastoma stem cells via the membrane receptor αvβ5, which is activated by the stem-specific transcription factor SOX2. Since the expression level of SOX2 is an important predictive marker for successful virotherapy, it is important to understand the fundamental mechanisms of the role of SOX2 in the dynamics of cancer stem cells and Zika viruses. In this paper, we develop a mathematical ODE model to investigate the effects of SOX2 expression levels on Zika virotherapy against glioblastoma stem cells. Our study aimed to identify the conditions under which SOX2 expression level, viral infection, and replication can reduce or eradicate the glioblastoma stem cells. Analytic work on the existence and stability conditions of equilibrium points with respect to the basic reproduction number are provided. Numerical results were in good agreement with analytic solutions. Our results show that critical threshold levels of both SOX2 and viral replication, which change the stability of equilibrium points through population dynamics such as transcritical and Hopf bifurcations, were observed. These critical thresholds provide the optimal conditions for SOX2 expression levels and viral bursting sizes to enhance therapeutic efficacy of Zika virotherapy against glioblastoma stem cells. This study provides critical insights into optimizing Zika virus-based treatment for glioblastoma by highlighting the essential role of SOX2 in viral infection and replication.