The new frontier of cancer research is in space

[MUSIC PLAYING] IRA FLATOW: Hi, it’s Ira Flatow, and you’re listening to Science Friday. Studying cancer and how tumors form is difficult. So that’s why some experts are taking their research off world.

SPEAKER 1: 5, 4, 3, 2, 1, ignition, and liftoff. Go SpaceX go NRL 172..

IRA FLATOW: Tumors will soon be sent to the International Space Station to see how they’ll grow and change in a weightless environment. It turns out that tumors grow in space at a startling rate. What would take 10 years on Earth to triple in size, in space takes just 10 days. So what does that mean for science and for the astronauts?

Two researchers behind those projects are here now to tell us why space is the new frontier for tumor research. Let me introduce them. Dr. Catriona Jamieson is a hematologist at the UC San Diego Health Moores Cancer Center, in California. And Dr. Meenal Datta studies the physics of cancer at the University of Notre Dame’s College of Engineering, in Indiana. Welcome to Science Friday.

CATRIONA JAMIESON: Thanks, Ira.

MEENAL DATTA: Thank you so much for having us.

IRA FLATOW: Nice to have you. Dr. Jamieson, here’s the million dollar question. What’s the benefit of taking cancer research to space?

CATRIONA JAMIESON: Well, I would say that’s a multi-billion dollar question. Because if we can solve this problem, it helps all of us. One in three of us is going to get cancer at one point in our lives, and everyone will have a family member or close friend who gets cancer.

But I would say cancer is a catalyst for cancer research. Because as you mentioned, Ira, in our experiments in Axiom 1, 2, 3, and 4 missions, and now what we’re launching with this NASA CASIS mission, we’re really aiming to see why cancer divides so quickly in space. Cancer seems to clone itself on steroids in space. So what we see is tripling in size of our tumor organoids in 10 days, when that would take 10 years on the ground to see the same thing.

IRA FLATOW: That is truly amazing. And we don’t know why that is. Is that right?

CATRIONA JAMIESON: Well, we’re getting a very good idea of why that is. So we see unleashing of what’s called the dark genome. So we have repetitive DNA, what we were told in undergrad was just junk, just ignore it. These repetitive elements vestigial viruses, leftover viral remnants in our DNA, they become activated under conditions of stress. And space is a mighty stressor to stem cells, but also to cancer. And we see that activates a gene called ADAR1, which has been under our radar for a long time, and we found a drug that can block it.

IRA FLATOW: I’d like to get back to that a little bit later. But first, Dr. Datta, you study the physics of cancer in space. Please tell me, is it hard to grow a tumor in the lab? Does it act the same way?

MEENAL DATTA: Yeah, this is one of the fundamental reasons that we actually use space, is because when researchers such as myself try to grow tumors in the lab, we try to grow these miniature 3D tumors that we call organoids. And unfortunately, they don’t form the same way that they do within the human body when we grow them in our Earth-based labs here at Notre Dame or at UC San Diego. And much of the work that’s been done in space to understand that organoids and 3D structures actually grow better in space have been done by Dr. Jamieson in her pioneering work over the last decade. And so that motivated us in our lab to start looking at cancer mechanics and the response of the immune system in space as well.

IRA FLATOW: Wow. My question here is, what is there in space? Is it really the zero gravity that helps this? I mean, is that really what it is?

MEENAL DATTA: Yeah, it turns out that gravity, as somebody who teaches aerospace and mechanical engineering classes– we have to talk about this all the time with our students– gravity is really a hindrance in our experiments on ground. It creates sedimentation and buoyancy and free convection that will compromise our ability to model cancer, to grow 3D tissues for regenerative medicine, and other advances such as that.

And so again, work by Dr. Jamieson and colleagues have shown that when you escape gravity– she uses this beautiful word “catalyst.” When you catalyze these experiments using space and the microgravity environment of space, we actually overcome those artifacts so that we can unmask some of the biology that we’re missing here on ground.

CATRIONA JAMIESON: Just to add to that very clever point, when you look at what happens with metastatic cancers, those cancers that spread to other sites, it’s as if they’ve escaped the bonds of Earth. They’ve escaped the bonds of their primary tissue, and they’re invading and metastasizing. And they need this three-dimensional structure that allows them to go forth and multiply.

And we’ve discovered that this sensor called Piezo1, P-I-E-Z-O-1, which was discovered by Ardem Patapoutian, at Scripps in San Diego, and got the Nobel Prize for that, is very important for this kind of biology. If Piezo1 is on, the cells think they need to stay at home in their normal microenvironment or niche. But if it gets switched off, they say, hey, let’s go forward. And that is what microgravity does as well.

IRA FLATOW: Wow. All right, so you’ve told us about how cancer cells, how cancers can grow so much faster in space. I mean, that raises the question for me that, what about the safety of astronauts? Could astronauts have undetected small cancers or blood cancers that they don’t know about? And suddenly, they go into space and zero gravity, and these things get sped up so quickly. Catriona, is that not a risk?

CATRIONA JAMIESON: I think it is a risk. It’s a risk for all of us on the ground as well. But in flight, so far when you look at astronauts, they’re pretty much superhuman. But for the rest of us, if we want to go up there, I think we do need to be careful about incipient malignancies, particularly blood cancers. Because blood cancers can lurk in the bone marrow with very few detectable signs till quite late in the course of disease.

Similarly, any cancer that tends to spread to the bone marrow would be hard to detect, based on just a simple blood test– metastatic breast cancer to the bone marrow, metastatic prostate cancer to the bone marrow. So I think it behooves us to do specialized testing. We were very grateful to be able to test the Axiom crew members from Axiom 2, 3, and 4, to see, are they getting stressed enough to actually activate inflammatory pathways that then allow incipient or precancerous lesions to become fully malignant?

So we studied their stem cells, and we discovered something sort of interesting. I thought it would be a Debbie Downer story, where everybody ages quickly at the stem cell level if they go into flight. And the editor of Cell Stem Cell, Sheila Chari, said, actually, that’s not what you’re seeing entirely. There was a resilience mechanism that seemed to be unleashed under conditions of stress in the astronauts, where they liberated a very regenerative, very good stem cell population to compete against the mutated stem cells.

So it’s sort of a Clone Wars situation, where resilience seemed to overcome that deterioration of the stem cells and the astronauts, something we didn’t expect to see. But it’s something we need to look at in all of us. Are we able to activate these resilience mechanisms that help to boost our immune responses against these early cancers or even pre-cancers? And that ended up being a very exciting and surprising discovery in the Axiom crew members.

IRA FLATOW: That is surprising. Meenal, are you surprised by that, too?

MEENAL DATTA: Well, nothing surprises me anymore in space. That’s what this research has taught me. But I think Dr. Jamieson raises a very important point, in that research has been going on in astronauts, in biological samples, in space for decades. And we are able to continue to build on those lessons learned.

So, for example, one of the findings that we found is that when we sent glioblastoma organoids to the Space Station on SpaceX 30 two years ago, we found that when we combine those cancer cells with immune cells that are present in human tumors, as well, those immune cells start to behave the same way that they do in the human body. They actually are reprogrammed by the cancer cells to help the cancer grow, rather than to fight against it.

And interestingly, those same molecular programs are turned on in astronauts in their circulating immune cells, indicating the suppressed immune system that has implications for multiple diseases. So all of that is to say that actually, space biomedicine allows us to better understand diseases here on Earth, even when we’re looking at two totally different disease profiles.

IRA FLATOW: Dr. Jamieson, you said earlier that your research has led to some treatment breakthroughs. Please tell me about that.

CATRIONA JAMIESON: Yes. So that drug is called Rebecsinib, named after Rebecca Moores. And it is a cancer kill switch. So if you’re not growing, you’re dying. We discovered that it stopped the tumor organoids from growing in our Axiom 3 launch.

And then we did Axiom 4 to test a number of tumor types, including the deadliest form of brain cancer, called glioblastoma multiforme; the deadliest form of acute myeloid leukemia, called secondary acute myeloid leukemia; the deadliest form of breast cancer, metastatic breast cancer; and ovarian cancer. So we saw that gene was upregulated in all four of those. And they are sensitive to this drug, Rebecsinib, which just finished its site initiation visit for the phase I clinical trial at the Moores Cancer Center at UC San Diego.

IRA FLATOW: So was this made possible, finding this drug that will stop the switch that turns on all these tumors, was this possible because you brought the tumors into space?

CATRIONA JAMIESON: We had already got enough data for myelofibrosis, a pre-leukemic, but pretty serious disorder, and then secondary acute myeloid leukemia on the ground. But what NASA allowed us to do on the International Space Station is to see, for other tumor types, whether they rely on this. Is this the Achilles heel for a broader array of cancers beyond blood cancers?

And I’m a hematologist, so I always focus on the blood. But in this case, we said, wait, maybe this is a bigger deal. And indeed, NASA allowed us to accelerate the research in other cancers. So as we move forward, we would like to actually start a phase Ib/II clinical trial for all ADAR-activated malignancies, based on space being a catalyst for cancer research, and giving us these data that allow us to look across a spectrum of cancers. So that was only made possible in the short time frame because of space.

IRA FLATOW: We have to take a quick break. But don’t go anywhere. We’ve got lots more when we come back.

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Meenal, I know you study a cancer that has no cure, and I’m talking about glioblastoma. Are you hopeful that doing research in space might help unlock the key to figuring this thing out?

MEENAL DATTA: I am very hopeful. As an engineer, I think we’re really attracted by these unsolvable problems. And glioblastoma is certainly one of them. And I really applaud Dr. Jamieson and her colleagues for being willing to welcome a non-traditional oncology researcher into their space, their research space, and real space, as well, such as myself. And I do think that bringing sort of out outside thoughts will open up some of this research as well.

Dr. Jamieson has already explained very nicely that space is accelerating our research and accelerating our pathway to cures, cutting down years or decades of research into a fraction of the time. And so I have no doubt that glioblastoma will benefit from the work that she and others have laid the groundwork for myself and newer researchers to build on. So what we will be sending in SpaceX 34, also with Space Tango, who is our implementation partner, as well, are patient-derived glioblastoma organoids, where we hope to better understand how their disease progressed, why they resist treatment.

And we will uncover additional targets beyond ADAR and similar pathways for testing as well. Our future flights later this year and beyond will be focused on drug testing against these patient-derived organoids as well. And to go to your question, Ira, about, What does the future hold for this? we have seen in this area that we’re now on the cusp of this commercial space era, moving forward into a new era and decade of research beyond the International Space Station, beyond these one-off investigations. And so as more commercial opportunities become available, this becomes an actual viable pipeline for research, to discovery, to clinical care.

IRA FLATOW: When you say commercializing this, does that mean you would send up just floating laboratories in orbit that you would do your research in? And would they be personed by astronauts, or would they be autonomous?

CATRIONA JAMIESON: I think both matter. I think natural intelligence trumps AI every time, because we learn things as a networked way of doing business, so to speak. Also, our neural stem cells are regenerative. So we learn, and then we amplify that learning together. So, so far, I think humans are beating machines.

What we do in the cube lab with Space Tango is a deeper dive into the molecular biology of what we’re looking at. So we did drug testing with Axiom. This one that we’re launching is SpaceX 34 was Space Tango’s, compared to metastatic breast cancer. So glioblastoma multiforme, highly invasive, nasty tumor, activates ADAR.

But what else is being fed to it by the surrounding so-called niche cells? And then similarly for metastatic breast cancer, does that behave differently? So we’re going to see in flight what happens in the human body when the immune system just isn’t working in your favor. And this is how our two experiments are really connected. And I would say we’re going to meet in the middle, right, Meenal?

MEENAL DATTA: I fully agree.

IRA FLATOW: I noticed that, Dr. Jamieson, you’re a hematologist. I mean, what other kinds of blood illnesses might be amenable for space medicine?

CATRIONA JAMIESON: Well, it’s so interesting that you asked that question. And Meenal was actually alluding to this. We see these inflammatory disorders. Think of autoimmune disorders, where you unleash this inflammatory cascade from your stem cells and your immune cells. And it actually starts from our stem cells, that give rise to all the immune cells.

When they go awry, you can actually fuel autoimmune disease or neuroinflammatory disorders, not just MS, but neurodegenerative disorders, like Parkinson’s disease, that affect 1.2 million people in this country, and also, multiple system atrophy, which my dad actually had. So what we find is that the stem cells under conditions of stress, inordinate stress, but also in conditions like space, for example, that unleash this inflammatory cascade, that seems to lead to neurodegeneration.

So I think we’ll learn a lot about all the processes that have to do with aging that we’d like to predict, prevent, and hopefully reverse if they’ve already happened. And this is not good aging. This is abnormal aging.

IRA FLATOW: One last question for you, Meenal. Tell me what it’s like to see your specimens launched. Do you feel like you’re sending your kids off to school for the first time?

MEENAL DATTA: I do think that actually, the more fun part is sending my students down to Kennedy Space Center, or to Cape Canaveral, because I literally feel like I’m launching these trainees into their future as space engineers who are, no doubt, going to work in this area. So I’m just as excited to see the students go down as the science.

IRA FLATOW: What a great place to end. I want to thank you both for taking time to be with us today. Dr. Meenal Datta studies the physics of cancer at the University of Notre Dame’s College of Engineering. Dr. Catriona Jamieson is a hematologist at the UC San Diego Health Moores Cancer Center, in California. Good luck to both of you and your research.

CATRIONA JAMIESON: Thanks, Ira.

MEENAL DATTA: Thank you, Ira.

CATRIONA JAMIESON: Go for lunch.

IRA FLATOW: This episode was produced by Kathleen Davis. And if you’re loving the show, let us know by giving us a five star rating. We’ll be back again tomorrow. See you then. I’m Ira Flatow.

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