Synergistic effects of bortezomib-OV therapy and anti-invasive strategies in glioblastoma: A mathematical model

Yangjin Kim, Junho Lee, Donggu Lee, Hans G. Othmer

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


It is well-known that the tumor microenvironment (TME) plays an important role in the regulation of tumor growth and the efficacy of anti-tumor therapies. Recent studies have demonstrated the potential of combination therapies, using oncolytic viruses (OVs) in conjunction with proteosome inhibitors for the treatment of glioblastoma, but the role of the TME in such therapies has not been studied. In this paper, we develop a mathematical model for combination therapies based on the proteosome inhibitor bortezomib and the oncolytic herpes simplex virus (oHSV), with the goal of understanding their roles in bortezomib-induced endoplasmic reticulum (ER) stress, and how the balance between apoptosis and necroptosis is affected by the treatment protocol. We show that the TME plays a significant role in anti-tumor efficacy in OV combination therapy, and illustrate the effect of different spatial patterns of OV injection. The results illustrate a possible phenotypic switch within tumor populations in a given microenvironment, and suggest new anti-invasion therapies.

Original languageEnglish (US)
Article number215
Issue number2
StatePublished - Feb 13 2019

Bibliographical note

Funding Information:
Funding: This paper was supported by Konkuk University in 2016: 2016-A019-0137 (Yangjin Kim)†.

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Copyright 2019 Elsevier B.V., All rights reserved.


  • Apoptosis
  • Bortezomib
  • CSPG
  • ER stress
  • Glioblastoma
  • Mathematical model
  • Oncolytic virus

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