Zika virus could be used to treat people with brain cancer
Zika can cause devastating effects. It has been linked with severe brain defects in unborn children and can lay dormant in carriers for months – but there may be a plus side.
By studying the spread of the virus in mice, researchers from St Louis have discovered Zika could be a viable treatment or even cure for brain cancer, namely glioblastoma.
Glioblastoma is a highly lethal, common cancer that can ravage the brain. Many patients die within two years of diagnosis and, just like normal, healthy tissues, the growth and development of glioblastomas is driven by stem cells that proliferate and give rise to tumour cells.
This makes glioblastoma stem cells (GSCs) especially hard to kill because they evade the body’s immune system and are resistant to chemotherapy and radiation. Yet killing these cells is vital to preventing new tumors recurring after the original tumor has been removed.
One approach to killing cancer stem cells involves using viruses that specifically target tumor cells and, given the impact Zika can have on normal brain cells, the team from Washington University School of Medicine in St. Louis and the University of California, San Diego explored whether the same effect would be seen on GSCs.
Zika virus (green) preferentially targets the stem cells (red) in a human glioblastoma
The standard ZIKV Dakar strains were provided by the World Reference Centre for Emerging Viruses and Arboviruses for the purposes of this study. The researchers discovered that these strains of Zika virus “preferentially infected and killed patient-derived glioblastoma stem cells compared with other glioblastoma cell types or normal neural cells”. Put more simply, the virus targeted and killed the stem cells over the other types of cells.
When mice with aggressive glioma were injected with a mouse-adapted strain of Zika virus, the virus slowed tumor growth and significantly extended the animals’ lifespan, typically by 10 days.
The researchers then tested a mutant strain of Zika that is less virulent than strains that occur naturally. It was generated from an infectious clone of a Cambodian strain of Zika.
This so-called “attenuated” strain, which is more sensitive to the body’s immune response, was still able to target and kill GSCs, and was even more effective when combined with a chemotherapy drug, temozolomide, that usually has little effect on these cells.
“Our results suggest that Zika is an oncolytic virus that can target GSCs; thus, genetically modified strains that further optimise safety could have therapeutic efficacy for adult glioblastoma patients,” explained the researchers.
Brain cancer stem cells (left) are killed by Zika virus infection (image at right shows cells after Zika treatment)
Study author Milan Chheda added: “It is so frustrating to treat a patient as aggressively as we know how, only to see his or her tumour recur a few months later. We wondered whether nature could provide a weapon to target the cells most likely responsible for this return.”
“This effort represents the creative synthesis of three research groups with complementary expertise to attack a deadly cancer by harnessing the cause of another disease,” continued fellow author Jeremy Rich. “Adults with Zika may suffer less damage from their infection, suggesting that this approach could be used with acceptable toxicity.”
The research is published in The Journal of Experimental Medicine. The team claims the research is a first step towards the development of safe and effective strains of Zika virus that could become important tools in neuro-oncology and the treatment of glioblastoma. The researchers added, however, that public health concerns will need to be addressed through pre-clinical testing and evaluations of the strains’ ability before it is used more widely.
Images: Wikimedia Commons/The Journal of Experimental Medicine/Zhe Zhu