Neurosurgeon Harry Bulstrode at the University of Cambridge, UK, is eager to research new treatments for glioblastoma, an aggressive yet common type of brain tumour. In May, he won a £200,000 (US$255,000) Cancer Research UK Pioneer Award to investigate whether the Zika virus, which has been linked to thousands of cases of microencephaly in newborns, offers a promising treatment pathway.
What attracted you to glioblastomas?
They are the most aggressive of primary brain tumours. Fewer than 5% of the 2,300 people diagnosed in England each year survive for 5 or more years. These tumours have rather unusual biology. They are mainly creatures of brain tissue; they don't usually spread throughout the body. All through my PhD programme, a recurring theme was the parallels between how glioma stem cells drive tumour development and how neural stem cells grow in fetuses. As a rule, adult brain cells don't display this rapid growth pattern. Glioblastoma tumours are the exception. My PhD work left one question unanswered — how to specifically target these tumour-causing cells.
How did you get the idea to test Zika as a possible brain-tumour treatment?
As soon as published papers confirmed that Zika caused specific damage to the developing brain while generally sparing mature cells, a light bulb went on for me. If the cancer cells resemble those in the developing brain, maybe Zika could attack them, too? If Zika could cross the blood–brain barrier and target glioma stem cells while passing by normal adult brain cells — two formidable hurdles for existing treatments — it could open up a way to use Zika to attack the tumour.
Did you seek advice from colleagues?
Yes. I dropped the idea into an e-mail to my PhD adviser, Steven Pollard. He said that it was an interesting idea, and reassured me that I wasn't crazy. Other mentors linked me up to a facility working with Zika and put me onto the Pioneer Award idea.
Are there concerns about your Zika research?
Pollard pointed out that any clinical trial could struggle to secure ethics approval to deliberately infect people with Zika. But I thought, why not explore the idea? Three million people have had this infection in the Americas. And adults who contracted it have almost universally made excellent recoveries or did not even notice the infection. I don't think it's a crazy idea to one day be able to offer the Zika virus or a modified version of it in a clinical trial to a person facing the prospect of death by brain tumour. But even before that step, this research offers interesting prospects for learning from Zika how to design potential therapies. A group at Cambridge recently published a study highlighting how Zika binds to a protein produced by neural stem cells, which simultaneously increases the viral turnover that leads to their destruction (http://dx.doi.org/10.1126/science.aam9243; 2017).et al. Science
How would you describe the risk level for this project?
The Pioneer Award is for high-risk projects. That said, I think this is quite a safe bet. The techniques are not revolutionary: cell cultures of tumour lines and neural stem cells are well established. The mouse models might be difficult to get right. Mice don't get Zika, so we'll need to work on how to give brain tumours and Zika to immune-compromised mice. If we can use Zika to show that tumours in the mice are smaller or ablated, that would be a huge result.
How might this project impact your career?
As an MD-PhD, my hope is to offer people with tumours the option of being involved in clinical trials. I think this project should help set me up well for that.
This interview has been edited for length and clarity.