How a Conversation
Over Dinner Might Change
the Way Brain Cancer Is Treated
During the Zika epidemic in the Americas, a registered nurse heard an interview, asked her husband a question, and set in motion the scientific program that became UP Oncolytics. This is the story of that question — and the biology that made it worth asking.
Brain Tumor Awareness Month exists, in part, because glioblastoma — the most aggressive primary brain cancer in adults — has resisted decades of determined scientific effort. Surgery, radiation, and chemotherapy have been refined, combined, and optimized. Median survival has barely moved. The disease remains, in the blunt language of oncology, nearly universally fatal.
We started UP Oncolytics because we believe there is a better way. And we found the first hint of it not in a laboratory, but over dinner, in the middle of a public health crisis on the other side of the world.
The Epidemic and the Interview
It was 2016. The Zika virus outbreak was spreading through Latin America and the Caribbean with frightening speed, and the news was dominated by its most devastating consequence: pregnant women infected with Zika were giving birth to infants with severe brain abnormalities, including microcephaly. Researchers were working urgently to understand why.
The answer, emerging in real time from laboratories around the world, was that Zika virus had an extraordinary and specific affinity for fetal neural progenitor cells — the stem-like cells responsible for building the developing brain. The virus entered these cells, replicated inside them, and destroyed them. The result, in the developing fetus, was catastrophic.
Amy Rovin, a registered nurse, heard an interview describing this mechanism. She turned to her husband, Richard — a neurosurgeon — and asked a question that was, in hindsight, both obvious and profound.
It was the right question at the right moment. And Richard knew immediately that it deserved a serious answer.
Why the Question Was Scientifically Sound
To understand why Amy's question landed so directly, it helps to understand what makes glioblastoma so difficult to treat — and what makes its biology so relevant to Zika.
Glioblastoma is diagnosed in approximately 15,000 Americans each year. The standard of care — surgery to remove as much of the tumor as possible, followed by radiation and chemotherapy — has not substantially changed since 2005. Median survival remains around 15 months. For patients and their families, that number is not a statistic. It is a horizon.
At the heart of GBM's lethal resilience is a subpopulation of cells called glioblastoma stem cells (GSCs). These self-renewing cells resist conventional therapy, drive tumor regrowth after treatment, and share a striking molecular resemblance to the fetal neural progenitor cells that Zika virus evolved to target — including the expression of many of the same surface receptors.
The parallel Amy had intuited was real. GSCs and fetal neural progenitor cells are not the same thing, but they are biologically related — similar enough in their receptor expression and cellular identity that a virus with high affinity for one might also target the other. The same properties that made Zika dangerous during fetal development could, in principle, be repurposed as a weapon against the stem cell population sustaining a GBM tumor.
A landmark 2017 paper from an independent research group confirmed the core premise: Zika virus could selectively infect and kill glioblastoma stem cells in laboratory models while largely sparing normal differentiated neurons in adult hosts. The biology was real. The question was how to develop it into a therapy.
Following the Science: The AXL Receptor
Understanding how ZIKV enters cells was essential to understanding whether and how it could be used therapeutically. The entry mechanism — the molecular doorway the virus uses to get inside a target cell — determines both the specificity of infection and the potential safety profile in adults.
For ZIKV to work as a therapeutic in adult GBM patients, it needed to preferentially target tumor cells over normal brain tissue. The key was identifying what made GBM cells susceptible — and what made healthy adult neurons resistant. If we could find a receptor that was abundant in the tumor and sparse in normal tissue, we would have the mechanistic basis for a selective therapy.
Our research identified the AXL receptor tyrosine kinase as the primary gateway for ZIKV entry into GBM cells. AXL is frequently overexpressed in glioblastoma — it plays a role in the tumor's invasive and immunosuppressive biology — while being far less abundant in normal, differentiated adult neural tissue. Critically, we found that AXL expression level directly predicts the magnitude of ZIKV infection: the more AXL a cell expresses, the more susceptible it is to the virus.
We went further to confirm the mechanism. Using CRISPR gene editing, we knocked out AXL in GBM cell lines — and found that ZIKV infection was completely abolished. Conversely, introducing AXL into cell lines that normally don't express it rendered those cells susceptible to infection. AXL is not merely one of several possible entry points. In GBM cell lines, it is the required gateway.
The implication is significant: a receptor that contributes to glioblastoma's aggressive behavior is also the door through which a therapeutic virus can enter. The tumor's biology becomes, in a sense, its own vulnerability.
Most adult GBM patients in the United States have never been exposed to Zika virus. Pre-existing immunity — which has hampered the clinical development of oncolytic candidates based on common viruses like herpes simplex and adenovirus — is unlikely to neutralize our therapeutic before it can engage the tumor. The relative immunological novelty of ZIKV in adult populations in temperate regions is, paradoxically, a clinical asset.
The Choice We Made: Wild-Type Over Engineered
With the biological rationale established, a critical decision awaited: what kind of virus would we develop?
Much of the oncolytic virotherapy field has pursued genetically engineered or laboratory-attenuated viral strains — viruses modified to reduce virulence or enhance tumor specificity. There is sound scientific logic to that approach. But it also introduces complexity: a genetically modified virus carries a different regulatory profile, a different manufacturing challenge, and a different set of unknowns than a naturally occurring strain.
We didn't want to engineer our way to safety. Nature had already solved part of the problem for us: Zika virus, while dangerous to the developing fetal brain, causes minimal neurological disease in healthy adults. The biology that makes it safe in adult hosts is inherent to the virus — not a property we needed to add in the laboratory. Our task was to find strains that expressed that natural safety profile most reliably.
Through our collaboration with the NIH, we identified wild-type ZIKV strains that are naturally, intrinsically minimally neurovirulent in adults. These strains' safety profile is a property of the virus itself — not the result of genetic modification. Their tolerability in human subjects has since been confirmed in a completed clinical trial, providing a human safety data anchor that strengthens the foundation for advancing into GBM studies.
From a Question to a Company
Amy's question led to a research program. The research program produced published findings. The published findings, combined with NIH SBIR Fast Track funding and a productive collaboration with the NIH, produced a clinical-stage asset with a documented safety profile and a well-characterized mechanism of action.
In October 2024, the FDA awarded Orphan Drug Designation to our ZIKV program for glioblastoma — a regulatory recognition that the science addresses a genuine unmet need, and that the development program merits the incentives the Orphan Drug Act was designed to provide. GBM, diagnosed in approximately 15,000 Americans annually, qualifies as a rare disease under federal law. It is also one of the most devastating diagnoses in medicine.
What Brain Tumor Awareness Month Means to Us
May is Brain Tumor Awareness Month — a time when the broader public is invited to understand the scale and urgency of what patients and families facing brain cancer confront every day. For us, it is also personal. The question that founded this company came from someone with a deep, professional commitment to patient care. A nurse who listened to an online interview, made a connection, and hoped it would help patients.
That is, at its core, how medicine advances. Not only through the systematic machinery of funded research and clinical trials — though that machinery is essential — but through moments of lateral thinking, through questions that cross disciplinary lines, through the willingness to ask whether something known in one context might apply in another.
Glioblastoma has defeated many well-resourced, well-designed attempts to improve on the standard of care. We do not underestimate what lies ahead. The path from a founding hypothesis to an approved therapy is long, expensive, and uncertain. But we believe the biology is real, the mechanism is sound, the safety foundation is established, and the regulatory framework is in place to support the work.
We are building something that started over dinner. This month, we are glad to share where it is going.