A ‘literal cancer moonshot:’ Researchers test oncology drugs in space
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UC San Diego researcher Catriona Jamieson, MD, PhD, likes to think of it as a “literal cancer moonshot.”
Jamieson and her colleagues are conducting several new nano bioreactor experiments aboard the International Space Station through the Axiom Space Private Astronaut Mission, Axiom Mission 2. The research adds to the team’s body of work on human stem cell aging, inflammation and cancer in low-Earth orbit.
“This is the first time any human cancer has been treated in space,” Jamieson, professor at UC San Diego School of Medicine and director of the Sanford Stem Cell Institute, told Healio. “The reason we like working in that low-Earth orbit environment is because it gives us insights into how cancer clones itself, and we can see it in a compressed timeframe — a shorter timeframe than it takes on Earth.”
Jamieson spoke with Healio about the unique mechanisms of cancer in low-Earth orbit, and discussed the implications of her research for future space travel and for cancer treatment.
Healio: What prompted this research?
Jamieson: The idea for studying how cancer evolves in space came from the NASA Twins Study, where Scott Kelly was in space for almost a year while his identical twin brother, also an astronaut, spent more of that time on the ground. Scott Kelly came back 2 inches taller but had changes in his blood. He had chromosomal inversions and translocations. He had telomerase activation. Telomerase is an enzyme that keeps our cells young, but you might not want that if the cells are premalignant. He then showed increased expression of inflammatory growth factors, or cytokines. The constellation of these three factors made me think that perhaps space accelerates aging in a malignant way. It may lead to precancer development.
So, we had the idea to send stem cells into space to see if they were corrupted by being in microgravity. When we started these experiments in December 2021 with a big NASA grant together with our partner, Space Tango, we noticed that normal-age stem cells do become exhausted in space compared with ground controls. We put the stem cells in a bioreactor — a pediatric blood bag that contained a sponge and the stem cells. Then we put in a fluorescent reporter of cell cycle activity to see if the cells were dividing. Based on the change in color, they divided way too quickly, and then they got exhausted.
So, then we said, “If normal stem cells get tired, does cancer get tired?”
On April 8, 2022, we decided to do this experiment, but this time with cancer cells. We put cancer cells in the same blood bag to see if they divide faster in microgravity. The answer was yes, if cancer cells get into microgravity, they divide faster, but they don’t stop. They just love that environment. They activate a cancer-cloning gene called ADAR-1, which becomes elevated in people with advanced blood cancers. ADAR-1 has been on our radar for a while, and we’ve been making a drug that we think blocks its capacity to be made into the most active version. It’s called rebecsinib after Rebecca Morris, PhD, whose name is on the cancer center.
There’s another drug that also dials down the activity of ADAR-1 — it’s an FDA-approved drug called fedratinib (Inrebic, Bristol Myers Squibb). We wanted to see if we could calm down cancer cell activity and, specifically, the formation of ADAR-1. So, we launched those tumor organoids into space in the bioreactor again, with this ADAR reporter that shows a fluorescent green signal if that is activated. We sent out blood bags, this time treated with either rebecsinib or fedratinib to see if we could shut off that gene if it got activated.
Healio: What did you find?
Jamieson: Peggy Whitson, PhD, the commander of the Axiom 2 Mission, is also a very experienced biologist and has studied cancer stem cells. She put the bioreactor on the microscope in space. We wanted to know whether we could reverse the activity of cancer stem cells. Our team, including Jessica Pham, went to Leidos in Houston, where the ground operations people control the microscope stage. It looks as though there might be a response in space already. We will be imaging several times at different timepoints to see if we continue to see this.
Everything in science has to be repeated to be rigorous, reproducible and reliable. So, we are hoping to work with Axiom and NASA in the future to do this more frequently. As of our latest experiment, it looks like we can block that cancer-cloning capacity, but this is the first time any human cancer has been treated in space. If you think of the major stressors that activate cancer, it looks like it is more microgravity related. Microgravity can reproduce the fight-or-flight response that the tissue-specific stem cells have when we’re stressed. I think that is what is happening. We’re not seeing radiation exposure effects — it looks primarily like microgravity.
Healio: Does this call the safety of space travel into question?
Jamieson: We should have testing to ensure it is safe. For some people, it may be fine. If you have a malignancy that’s dormant, [space travel] may be the boost that malignancy needs to take off. However, we can develop predictive tools for that. We can do blood tests; we can do scanning if people plan to go into space to live, work or play there. What we’ve learned is that some people are OK — if we can predict, prevent or reverse this, it’ll be fine.
Healio: Is there anything else you’d like to say?
Jamieson: NASA has been very engaged and NCI is very excited about these studies. The experiments will come back after about 10 days in space, and then we’ll do whole transcriptome sequencing and look at the cells to see if they behave differently. We’ll be imaging again three more times, but this unusual partnership in this unusual environment is accelerating our ideas into how cancer develops. We’re very grateful to NASA, to the NCI and to the patients who are willing to give their blood and bone marrow for these experiments.
For more information:
Catriona Jamieson, MD, PhD, can be reached at UC San Diego, 9500 Gilman Drive, La Jolla, CA 92093; email: cjamieson@ucsd.edu.
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Healio Interviews
The future of drug discovery may be in space. UC San Diego’s new astrobiotechnology hub is set to explore it (press release). Available at: https://www.universityofcalifornia.edu/news/future-drug-discovery-may-be-space-uc-san-diegos-new-astrobiotechnology-hub-set-explore-it. Published March 3, 2023. Accessed May 23, 2023.
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