Zika Virus: A New Therapeutic Candidate for Glioblastoma Treatment

Abstract

Glioblastoma (GBM) is the most aggressive among the neurological tumors. At present, no chemotherapy or radiotherapy regimen is associated with a positive long-term outcome. In the majority of cases, the tumor recurs within 32–36 weeks of initial treatment. The recent discovery that Zika virus (ZIKV) has an oncolytic action against GBM has brought hope for the development of new therapeutic approaches. ZIKV is an arbovirus of the Flaviviridae family, and its infection during development has been associated with central nervous system (CNS) malformations, including microcephaly, through the targeting of neural stem/progenitor cells (NSCs/NPCs). This finding has led various groups to evaluate ZIKV’s effects against glioblastoma stem cells (GSCs), supposedly responsible for GBM onset, progression, and therapy resistance. While preliminary data support ZIKV tropism toward GSCs, a more accurate study of ZIKV mechanisms of action is fundamental in order to launch ZIKV-based clinical trials for GBM patients.

Zika virus cleaves GSDMD to disseminate prognosticable and controllable oncolysis in a human glioblastoma cell model

“…ZIKV seems preferentially harmful to the neurons of fetuses and children 35 but seldomly adults, so pathogenic ZIKV infection could be a potential oncolytic therapy against adult GBM. 36 , 37 However, a safe and aspirational viral therapy requires investigation of the mechanism of how, beyond the phenotypic observations, the virus causes specific cell death. Here, we showed that ZIKV could be an oncolytic virus by killing human GBM via viral protease-mediated GSDMD activation.…”

microRNAs (miRNAs) in Glioblastoma Multiforme (GBM)—Recent Literature Review

“…miR-34c can be used to treat GBM or other types of cancer. This particular miRNA can be successfully transmitted by viral vectors or extracellular vesicles [ 129 ].…”

Therapeutic Applications for Oncolytic Self-Replicating RNA Viruses

“…As CICs have been shown to be resistant to conventional anticancer therapies, the potential of oncolytic viruses to destroy CICs have made them attractive for alternative therapeutic applications. Oncolytic viruses of different origin [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ] comprise wild-type viruses, which are unable to infect normal cells but are cytotoxic to cancer cells [ 17 ]. Moreover, the deletion of viral genes critical for replication in normal cells but dispensable in cancer cells has generated attenuated oncolytic strains.…”

“…Additionally, Aura virus (AURAV) has shown oncotropism for certain tumor cell lines [ 27 ]. In the context of flaviviruses, the Zika virus (ZIKV) has demonstrated oncolytic activity against glioblastoma stem cells (GSCs) [ 14 , 28 ]. The negative-stranded measles viruses (MV) have also demonstrated oncolytic activity in several preclinical studies [ 15 ].…”

“…Different types of viruses such as adenoviruses [ 9 ], alphaviruses [ 8 ], Herpes simplex viruses [ 10 ], rhabdoviruses [ 11 ], Newcastle disease virus [ 12 ], and vaccinia viruses [ 13 ] have demonstrated oncolytic properties. However, in this review, the focus is entirely on oncolytic viruses belonging to the families of self-replicating RNA viruses such as alphaviruses [ 8 ], flaviviruses [ 14 ], measles viruses [ 15 ], and rhabdoviruses [ 11 ]. The self-replication of viral RNA and the application of oncolytic self-replicating RNA viruses in preclinical animal models and in clinical trials on cancer patients are described.…”