Editors' ChoiceCancer

Foe becomes friend as Zika joins the fight against cancer

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Science Translational Medicine  27 Sep 2017:
Vol. 9, Issue 409, eaao6888
DOI: 10.1126/scitranslmed.aao6888

Abstract

Zika virus preferentially targets cancer stem cells in glioblastoma, resulting in reduced tumor growth.

The headlines regarding Zika virus in the recent past would leave one convinced that this virus can lead only to devastation, not a potential therapeutic breakthrough for one of the most deadly brain tumors, glioblastoma. However, Zhu et al. have demonstrated just that by capitalizing on Zika’s proclivity to infect immature neuronal cells of the developing central nervous system. These exact cells are absent in the adult brain, but glioblastoma depends on a subpopulation of tumor cells for continued growth, called glioblastoma stem cells (GSCs), which share many similarities to these developmental neuronal precursors.

Recognizing this, the authors saw a unique opportunity to explore if Zika would have antitumoral activity by preferentially infecting and killing GSCs. This approach, called oncolytic viral therapy, is based on using viruses that preferentially replicate in and hence obliterate tumor cells over normal cells and is currently being explored for glioblastoma using other genetically engineered viruses (but had not previously been investigated for Zika). Using multiple models (purified GSCs, a 3-dimensional organoid system, and human glioblastoma tissue slices), they confirmed that Zika could specifically target GSCs. Importantly, limited toxicity to normal brain tissue was detected. Also relevant to the future clinical utility of this approach, a less potent strain of Zika virus was able to kill GSCs. This attenuated Zika strain was also tested in combination with temozolomide, a chemotherapeutic currently used for glioblastoma treatment. Normally GSCs do not respond to temozolomide but when used in combination with the attenuated Zika strain, there was greater cell death than when either treatment was used alone. The authors then went on to test Zika in mouse models of glioblastoma, using a form of Zika that could infect mouse cells, and observed preferential infection of GSCs, reduced tumor growth, and extended survival of Zika-treated mice.

These results provide the first evidence that Zika is a viable option to use in combination with conventional therapeutics, which fail to target GCSs, as a means to eradicate the entire tumor. Reaching this point will of course require extensive examination into safety, including potential toxicity to human adult neural stem cells, as well as elucidation of what dictates specificity toward GSCs. Nonetheless, with no current curative therapies for glioblastoma, this seemingly unconventional approach offers an exciting avenue for further exploration.

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