Zika virus could be used to treat brain cancer, new study suggests

The same mechanism that damages developing brains allows Zika virus to target cancer stem cells.

It’s well known that Zika virus is dangerous for developing brains, but new research suggests it could actually benefit adult patients with brain cancer. Glioblastoma, the most common type of brain cancer, is usually lethal, as surgically removed tumors typically regrow in a few months. The growth of glioblastoma tumors is driven by stem cells, similar to the growth of healthy tissue in a developing brain. In a new study, researchers injected Zika virus into the brain tumors of mice to test its effectiveness as a potential cancer treatment. The initial results are promising, with treated mice living two to three times longer than those that weren’t injected with the virus. One of the study’s authors, Milan Chheda of the Washington University School of Medicine, tells us more.

ResearchGate: What is glioblastoma?

Milan Chheda: Glioblastoma is an aggressive brain tumor. It originates in the brain, and does not usually metastasize outside of the central nervous system. It kills most people in less than two years of diagnosis despite maximal therapy with surgery, radiation, and chemotherapy.

RG: What challenge in treating this type of cancer does your research address?

Chheda: Despite the most aggressive treatments possible, the tumor inevitably returns. Glioblastoma stem cells are resistant to radiation and chemotherapy. A longstanding challenge has been how to specifically kill these otherwise resistant cells. No current therapy specifically eradicates these cells.

RG: What made you think the Zika virus might help with this?

Chheda: Brain tumor stem cells activate many pathways similar to early stage neuroprogenitors. Normally, Zika virus has a tropism for neuroprogenitor stem cells in the developing fetus. Zhe Zhu, a postdoctoral fellow in Jeremy Rich’s laboratory, reasoned that since Zika can target these neuroprogenitor cells, it might also target cancer stem cells, which share similarities to these cells.

RG: How did you test this in mice?

Chheda: We implanted highly aggressive mouse glioma cells in mouse brains. After brain tumors formed, we treated the mice by directly injecting mouse-adapted Zika virus into the tumor.

RG: What were the results?

Chheda: Mice treated with Zika virus lived significantly longer. In one mouse model, mice lived two times longer after treatment compared to mice treated with saline control. In another mouse model, mice lived three times longer after treatment compared to controls. When we inspected mouse brains, we found that the virus did not spread outside of the tumor.

Zika virus (green) preferentially targets the stem cells (red) in a human glioblastoma. Credit: Zhu et al., 2017

RG: How likely is it that this success would translate to humans?

Chheda: We have guarded optimism. But we need to further test safety and we need to prove this works in human glioblastomas when transplanted into mice.

RG: Were there negative effects? What are the dangers?

Chheda: We did not see negative effects of the virus in the mice. Potential dangers are that the virus could injure normal brain or spread. We are currently testing attenuated virus in mice. However, Zika virus does not typically cause significant problems in adults.

RG: What are the next steps for this research? Could a human trial be on the horizon?

Chheda: We are focused on developing and testing safer versions of the virus, and testing the therapy in mice carrying human tumors. After this, yes, we envision tests in humans, and eventually adding this to existing conventional therapy (surgery, radiation, and chemotherapy) to kill the otherwise resistant stem cell component of the tumor.