Synergistic Effects of Bortezomib-OV Therapy and Anti-Invasive Strategies in Glioblastoma: A Mathematical Model

Area of Science:

• Oncology
• Mathematical Biology
• Virology

Background:

• The tumor microenvironment (TME) is crucial for tumor growth and therapy response.
• Combination therapies, including oncolytic viruses (OVs) and proteasome inhibitors, show promise for glioblastoma.
• The TME's role in OV and proteasome inhibitor combination therapy remains understudied.

Purpose of the Study:

• To develop a mathematical model for combination therapy using bortezomib and oncolytic herpes simplex virus (oHSV).
• To investigate the TME's influence on bortezomib-induced endoplasmic reticulum (ER) stress.
• To understand how treatment protocols affect the apoptosis-necroptosis balance.

Main Methods:

• Development of a mathematical model simulating OV and bortezomib interactions.
• Analysis of the TME's impact on treatment efficacy.
• Simulation of different spatial patterns for OV injection.

Main Results:

• The TME significantly affects the anti-tumor efficacy of OV combination therapy.
• Spatial injection patterns of OVs influence treatment outcomes.
• The model illustrates potential phenotypic switching in tumor populations within the TME.

Conclusions:

• The TME is a critical factor in the success of oncolytic virus and bortezomib combination therapies for glioblastoma.
• Understanding TME dynamics can optimize treatment strategies.
• Findings suggest novel anti-invasion therapeutic approaches targeting tumor microenvironment interactions.