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

Cancers

Junho Lee¹  Yangjin Kim¹  Donggu Lee¹  HansG. Othmer² 

[1] Department of Mathematics, Konkuk University, Seoul 05029, Korea;School of Mathematics, University of Minnesota, Minneapolis, MN 55455, USA;

关键词: glioblastoma;    oncolytic virus;    mathematical model;    bortezomib;    ER stress;    apoptosis;    CSPG;   

DOI  :  10.3390/cancers11020215

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown