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 language | English (US) |
|---|---|
| Article number | 215 |
| Journal | Cancers |
| Volume | 11 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 2019 |
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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 journal › Article
}
TY - JOUR
T1 - Synergistic effects of bortezomib-OV therapy and anti-invasive strategies in glioblastoma
T2 - A mathematical model
AU - Kim, Yangjin
AU - Lee, Junho
AU - Lee, Donggu
AU - Othmer, Hans G.
PY - 2019/2
Y1 - 2019/2
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Bortezomib
KW - CSPG
KW - ER stress
KW - Glioblastoma
KW - Mathematical model
KW - Oncolytic virus
UR - http://www.scopus.com/inward/record.url?scp=85062675127&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062675127&partnerID=8YFLogxK
U2 - 10.3390/cancers11020215
DO - 10.3390/cancers11020215
M3 - Article
C2 - 30781871
AN - SCOPUS:85062675127
VL - 11
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 2
M1 - 215
ER -