July 9, 2021

Out of this world: How space radiation research at UW is creating real-world applications here at home

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Madison, Wis. — Space can be a pretty unforgiving place. In addition to the lack of oxygen, freezing cold temperatures and flying space debris, there’s also the high-energy space radiation. Without an atmosphere for protection, astronauts are more exposed to radiation from the sun and other sources; however, high-energy radiation’s effect on humans, and how it varies from person-to-person, isn’t fully understood.

But ongoing space radiation research – including contributions from one UW Carbone Cancer Center member – is helping NASA better understand the cancer risk associated with interplanetary space travel.

It’s research that not only has implications for astronauts heading to Mars, for example, but also for cancer patients in the clinic here on Earth.

Nearly two decades ago, Richard Halberg, PhD, began working with Jeff Bacher, PhD, at the Promega Corporation. Bacher had just received his first grant from NASA to study radiation exposure and needed someone to handle the mouse models.

Since then, the two have maintained a steady collaboration and have landed a handful of additional NASA grants to build upon their work.

Unsurprisingly, space radiation is a bit tricky to study. You can’t easily send humans into space, nor can you easily or ethically expose them to the kind of high atomic number, high-energy (HZE) radiation they’d find beyond our atmosphere. But at NASA Space Radiation Laboratory at Brookhaven in New York, you can simulate the effect of this radiation, in a controlled environment, using mice.

Previous studies there have shown that exposure to this high-energy radiation causes tumors in mice. Many of these studies have also suggested these tumors would be much more aggressive, or metastasize to other sites in the body.

But in their latest study, published in the International Journal of Radiation Biology, Halberg and Bacher found that hypothesis didn’t exactly hold up when it came to liver tumors, in particular. Using the tools at Brookhaven and a fluorescent reporter to effectively light up and track cancer cells, the two were able to see where the tumors were in the livers of the irradiated mice, but also allowed them to look for circulating tumor cells or metastatic lesions in nearby organs or tissues.

“What we found is that the radiation still induced liver tumors, but it didn’t induce more aggressive tumors,” Halberg said. “We did see a slight increase in the number of tumors that formed, but they were not any more aggressive than tumors that had formed after exposure to this low energy radiation, or just those that spontaneously formed.”

A research colleague at another institution also found a similar result when studying radiation-induced mammary tumors in mice.

It’s not to say that their combined results contradict past research. Previous studies have focused on other types of tumors, such as colon cancer. Halberg says additional studies targeting additional cancer types will likely have to be the next step to fully answer the aggressiveness question.

While it might feel like an unsatisfying result, Halberg says there’s a huge positive that came out of this study: the mouse model developed for the project actually turned out to be a good model for understanding liver cancer in humans.

“Many of the molecular features of the tumor, and many of the clinical tests that would be run, our mouse models actually mimicked what would happen in the clinic essentially,” he said.

One striking example of that involves a protein called alpha-fetoprotein. Found in the blood, alpha-fetoprotein is considered a biomarker for liver cancer in humans. In their research, Halberg and Bacher collected blood samples from the mice as they were aging. They found that not only could the protein also be detected in mouse blood, but it could also predict outcomes.

“The level of alpha-fetoprotein increased in mice that eventually developed cancer and stayed low in mice that didn’t develop cancer,” Bacher said. “By testing the blood, you can pretty much determine which mice will develop liver cancer in the future.”

It stands to reason that this mouse model could potentially be used in the future testing for new liver cancer therapeutics.

Throughout their now five grants together, both Halberg and Bacher have learned to embrace the unexpected. Their space radiation work has led to additional “spin-off” studies, using their models and markers to explore things like personalized doses of radiation, the effect of multiple CT scans on cancer risk, and better predicting which patients might have a better response to certain immunotherapy drugs.

“This is the serendipity, the spin-offs you didn’t anticipate 20 years ago when you started a project,” Halberg said.

So even if humans aren’t heading to Mars anytime soon, the impact of Halberg and Bacher’s space radiation research will have a much more immediate impact, and arguably in a more important place, right here on Earth.