TY - JOUR
T1 - The complex relationship between integrins and oncolytic herpes Simplex Virus 1 in high-grade glioma therapeutics
AU - Rivera-Caraballo, Kimberly Ann
AU - Nair, Mitra
AU - Lee, Tae Jin
AU - Kaur, Balveen
AU - Yoo, Ji Young
N1 - Publisher Copyright:
© 2022 The Author(s)
PY - 2022/9/15
Y1 - 2022/9/15
N2 - High-grade gliomas (HGGs) are lethal central nervous system tumors that spread quickly through the brain, making treatment challenging. Integrins are transmembrane receptors that mediate cell-extracellular matrix (ECM) interactions, cellular adhesion, migration, growth, and survival. Their upregulation and inverse correlation in HGG malignancy make targeting integrins a viable therapeutic option. Integrins also play a role in herpes simplex virus 1 (HSV-1) entry. Oncolytic HSV-1 (oHSV) is the most clinically advanced oncolytic virotherapy, showing a superior safety and efficacy profile over standard cancer treatment of solid cancers, including HGG. With the FDA-approval of oHSV for melanoma and the recent conditional approval of oHSV for malignant glioma in Japan, usage of oHSV for HGG has become of great interest. In this review, we provide a systematic overview of the role of integrins in relation to oHSV, with a special focus on its therapeutic potential against HGG. We discuss the pros and cons of targeting integrins during oHSV therapy: while integrins play a pro-therapeutic role by acting as a gateway for oHSV entry, they also mediate the innate antiviral immune responses that hinder oHSV therapeutic efficacy. We further discuss alternative strategies to regulate the dual functionality of integrins in the context of oHSV therapy.
AB - High-grade gliomas (HGGs) are lethal central nervous system tumors that spread quickly through the brain, making treatment challenging. Integrins are transmembrane receptors that mediate cell-extracellular matrix (ECM) interactions, cellular adhesion, migration, growth, and survival. Their upregulation and inverse correlation in HGG malignancy make targeting integrins a viable therapeutic option. Integrins also play a role in herpes simplex virus 1 (HSV-1) entry. Oncolytic HSV-1 (oHSV) is the most clinically advanced oncolytic virotherapy, showing a superior safety and efficacy profile over standard cancer treatment of solid cancers, including HGG. With the FDA-approval of oHSV for melanoma and the recent conditional approval of oHSV for malignant glioma in Japan, usage of oHSV for HGG has become of great interest. In this review, we provide a systematic overview of the role of integrins in relation to oHSV, with a special focus on its therapeutic potential against HGG. We discuss the pros and cons of targeting integrins during oHSV therapy: while integrins play a pro-therapeutic role by acting as a gateway for oHSV entry, they also mediate the innate antiviral immune responses that hinder oHSV therapeutic efficacy. We further discuss alternative strategies to regulate the dual functionality of integrins in the context of oHSV therapy.
KW - FAK
KW - GBM
KW - TME
KW - focal adhesion kinase
KW - glioblastoma
KW - integrins
KW - oHSV
KW - oncolytic herpes simplex virus 1
KW - tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85132943302&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85132943302&partnerID=8YFLogxK
U2 - 10.1016/j.omto.2022.05.013
DO - 10.1016/j.omto.2022.05.013
M3 - Review article
AN - SCOPUS:85132943302
SN - 2372-7705
VL - 26
SP - 63
EP - 75
JO - Molecular Therapy - Oncolytics
JF - Molecular Therapy - Oncolytics
ER -