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 journalArticle

1 Citation (Scopus)

Abstract

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
JournalCancers
Volume11
Issue number2
DOIs
StatePublished - Feb 2019

Fingerprint

Oncolytic Virotherapy
Glioblastoma
Theoretical Models
Tumor Microenvironment
Oncolytic Viruses
Neoplasms
Therapeutics
Endoplasmic Reticulum Stress
Simplexvirus
Clinical Protocols
Bortezomib
Apoptosis
Injections
Growth
Population

Keywords

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

Cite this

Synergistic effects of bortezomib-OV therapy and anti-invasive strategies in glioblastoma : A mathematical model. / Kim, Yangjin; Lee, Junho; Lee, Donggu; Othmer, Hans G.

In: Cancers, Vol. 11, No. 2, 215, 02.2019.

Research output: Contribution to journalArticle

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