Research at Sanford Stem Cell Institute Examine Effects of Targeted Cancer Treatments in Space

A group of scientists are conducting an investigation funded by the International Space Station (ISS) National Laboratory to help understand how cancer spreads and enhance treatments for patients on Earth by sending cancer organoids into space. Cancer is the second leading cause of death globally, an issue close to the hearts of many people in the US.

Researchers from the University of California San Diego and the Sanford Stem Cell Institute are joining forces with Axiom Space to conduct a study of cancer stem cells. These special cancer cells are the catalysts of cancer growth and relapse, and the research team will be observing them as they regenerate over time.

Axiom Space’s second private astronaut mission (Ax-2) will build on the findings from its previous mission in 2022. This mission sent three-dimensional intestinal cancer organoids into space inside a nano bioreactor. The research conducted during this mission found that tumour stem cells grow extremely quickly in a microgravity environment, tripling their size in only 10 days. Furthermore, it was unveiled that the cells activated an enzyme called ADAR1. This enzyme is associated with RNA1, and it allows cancer cells to clone themselves, making them resistant to therapies that target dividing cells, and thus, evade the body’s immune response.

“We want to know if ADAR1 is activated as a stress response to microgravity and if it gets turned on in other types of cancers,” said Catriona Jamieson, professor of medicine at UC San Diego and Sanford Stem Cell Institute director. “So, we will be sending three types of tumor cells into space this time, looking at not only intestinal cancer but also leukemia and breast cancer cell organoids.” The team will investigate how the cell cycle and ADAR1 expression are affected in tumor organoids and whether therapies that reduce ADAR1 activity, such as fedratinib (Inrebic®) and rebecsinib, are effective.

The Ax-2 mission seeks to explore the effect of ADAR1 inhibitors on malignant regeneration by monitoring cellular changes in tumour organoids. Through a high-resolution fluorescence microscope, the crew will document the cell cycle and ADAR1 activity in order to identify biomarkers for early cancer detection. The findings from this research could serve as a fighting chance against cancer and will help shape future research on cancer stem cells both on Earth and in space.

Jamieson believes the results of this experiment could provide insight into whether ADAR1 is a ubiquitous stress response that enables cancer cells to replicate themselves and if the enzyme can be inhibited by drugs such as fedratinib (Inrebic®) or rebecsinib.

“Metastasis occurs when cancer decides to invade and spread to other parts of the body,” Jamieson said. “ADAR1 is a strong trigger to invade or metastasize, which is what we’re trying to switch off.”

Jamieson is very excited to investigate the way human cells function in an ultimately difficult place such as microgravity. The research could be more accurate on human cancer cells in contrast to animals, by sending three-dimensional tumor organoids into space. “We are thrilled to study how human cells work in a uniquely stressful environment like microgravity,” she said. “When we compare this to what happens on Earth, we’re seeing that this recapitulates what we see when cancers spread.”

The research team has the opportunity to test if it is possible to turn off ADAR1 by conducting their studies on shorter timescales due to the fact that cancer stem cells grow more quickly in space.

“Microgravity speeds up the ageing process and allows us to see things in just 10 days that happen over longer periods of time on Earth,” Jamieson said. “So, these experiments are allowing us to study not only accelerated ageing from a stem cell standpoint but also at what point cells start to become pre-malignant and fully malignant.”

As part of the Ax-2 mission, the team is also sending a second project to space, to study the effects of microgravity-induced stem cell ageing on the four Ax-2 astronauts over a period of five years.

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