E42: Beyond Survival: AI, Immunology, and the Investment in a Cure with Susanna Greer

In this episode, Dr. Timothy Chou speaks with Dr. Susanna Greer of the V Foundation about the unique biology and challenges of pediatric cancer—and why children require fundamentally different approaches than adults. They explore how philanthropy, early-stage research funding, and AI-driven insights are accelerating breakthroughs, from precision treatments to faster clinical trials. Greer shares a compelling vision for the future, where cancer care is more personalized, less toxic, and accessible regardless of where a child lives.

This episode is brought to you by BevelCloud—powering distributed AI in healthcare and driving the Pediatric Moonshot forward. Learn more at BevelCloud.ai."

Transcript

SPEAKER_01 0:03

Good morning, good afternoon, good evening to everyone to another edition of the Pediatric Moonshot Podcast series. Really pleased today to have Dr. Susanna Greer, who is Chief Scientific Officer at the V Foundation for Cancer Research. She's a former senior scientific director at the American Cancer Society, previously a Georgia Cancer Coalition Distinguished Cancer Scholar and a tenured professor at Georgia State. She got her PhD in immunology from the University of Alabama at Birmingham and did postdoc training at the University of North Carolina, Chapel Hill, Gotar Hills. So with that, welcome.

SPEAKER_00 0:48

Thank you so much, Timothy. Gotar Hills indeed. Yeah, being from the Deep South, I didn't realize uh what it would be when I got to UNC. But it's it's a real pleasure to join you. Um Pediatric cancer research is an area where progress has been hard won and where urgency still defines our work every day. So thrilled to be here.

SPEAKER_01 1:11

Uh let's start with a question you kind of kicked it off with me. I never thought about it. It's like, how'd you get from immunology to cancer?

SPEAKER_00 1:19

Oh, that's a great question. Um I think this is something a lot of people who aren't immunologists don't think about all the time. But if you are in this field, a really simple way to think about the immune system is and diseases in which the immune system is directly involved, is that autoimmune disease, which I studied for many, many years, uh, is largely an overreaction of the immune system, where we think about our immune system attacking tissues that it shouldn't. So in diseases like multiple sclerosis or Crohn's disease or diabetes. Um in direct comparison, cancers you can we can largely think of um as an under-reaction of the immune system, meaning that cancer cells really only do one thing that normal cells don't do. They divide indefinitely. Normal cells have a finite half-life. And the way that cancer cells are able to divide indefinitely is they, through genetic mutations, develop proteins that are different than normal cells. Um and if we are lucky enough to have never had a cancer diagnosis, it means that our immune systems are detecting those proteins all the time and eliminating cancers. If we have a diagnosis at some level, the immune system has failed in that way. So your question is, how do I get to be a cancer researcher? So I was studying autoimmune disease and made some discoveries as a fellow that directly applied to cancer, and that was the start of my career in cancer research.

SPEAKER_01 3:02

Out of curiosity, did you specialize in some area within cancer?

SPEAKER_00 3:07

Absolutely. So uh in science, we think about your expertise being in developmental science. Some people call it basic science, but it's anything versus basic. It's more like thinking about what does this gene do? What does this protein do? Then we translate that into animal models and we move it into the clinic. My research was on the developmental side, and I was trying to understand why the immune system miss those signals and how are cancers are so smart, how are cancers able to hide from the immune system? But the model systems that I used were breast and colorectal cancer, where the immune system is particularly good at um missing cancers for lots of reasons. This podcast, I think, is like 20 minutes. Do you have two years? Because we could do a basic analogy course. I think your listeners would love it. I think they'd love it. Yeah. Yeah, keep going. It's free. I mean, I'm here all day, folks. I'm here all day. But yeah, that that's really kind of the basis of it is that I was thinking about in a big space, how are tumors able to hide from the immune system so well? How are they so tricky? And then how can we apply the things that I was learning in specific cancers where they were able to do that exceedingly well? And colorectal and breast are a great example of that. So I used animal models to move that research into the clinical space.

SPEAKER_01 4:36

Is there any, I mean, I is there any overlap between, as you pointed out, these are two sides of the same coin. Is there any overlap between research in autoimmune and cancer?

SPEAKER_00 4:47

Yeah, absolutely. The more that we learn about ways to enhance the immune response, and there are hundreds of ways that we can understand how what is a cancer cell, I mean, sorry, what is an immune cell quote unquote missing that it's just not seeing? What kind of signals? Um, and then how do we enhance that? And on the flip side, there are things that tumors actually do to turn off the immune system. So all of those things involve proteins, and many of them involve genes that are mutated during cancer. So the reverse of that is absolutely true. That when we think about autoimmunity, we want to shut those things down. So that's exactly how I got into this field is in autoimmune disease and specifically multiple sclerosis, I was understanding what is it about a glial cell in the brain that is so attractive, for lack of a better word, to the immune system. And why do we have this attack in the immune system during multiple sclerosis and how might we suppress that? And so transversely, we think about how we might activate some of those signals in cancer cells. Yeah. So it's it's fundamentally an inverse. I mean, there I am any immunologist who is listening to this is probably about to have a heart attack. I am vastly overstating, but it is quite true, right? I mean, there are so many hundreds of complexities, but it it is how the field has moved so quickly, I think, honestly, in in cancer research um and immunotherapy is our understanding of autoimmune disease. Yeah.

SPEAKER_01 6:25

Wow. Wow. Uh, you know, we talked earlier, and I I have to say I was surprised at how much the V Foundation funds pediatric cancer research, because obviously I had always thought about it as adult cancer. So could you talk a little bit about that?

SPEAKER_00 6:40

Yeah, absolutely. I'd be happy to talk to you about that. So uh the V Foundation, as uh your listeners may or may not know, we have a hundred percent giving pledge, and so we are really driven by um our donors' desires. Um, if a dollar comes in the door for research, we deploy it according to what our um donors are excited about and interested in or how they've been impacted by cancer. So what Timothy is referring to is that we um I would say work quietly behind the scenes in many ways, but since our founding, 31 years ago, so not that long ago, we've awarded over 458 million in cancer research funding. And that includes uh more than 107 million that was directed specifically to pediatric cancer. And I think honestly, the what is almost in some ways more important than that, those dollars, is how they're used. Uh at the V Foundation, we pride ourselves on funding really exceptional scientists pretty early in their careers, um, often at moments when federal funding is isn't yet available to them, or that they are in the that process of applying for federal funding. And that so that early support has what I think of as kind of a multiplier effect. Um our V-funded pediatric researchers, so just that cohort that have received that 107 million, have gone on to secure more than $2.3 billion in additional funding, uh, and that is directly correlated to their V Foundation work, and they have contributed to nearly 200 pediatric uh clinical trials. So while that initial investment might surprise people, 107 million, it's a big number. It's almost a fourth of our research budget. The long-term impact, I think, is equally exciting because we are showing how philanthropy can accelerate uh pediatric research in that ecosystem.

SPEAKER_01 8:44

Could you talk a little bit about what what is unique about pediatric cancer versus adult cancer?

SPEAKER_00 8:49

Oh, I love that question. Um so uh one of the challenges that we have in pediatric research is that children are not just mini adults, right? So that's something that that you you may hear a lot. Um I think that so there's several different ways that pediatric cancer is different than adults. One is the biology is completely different. Um, adult cancers, um, if we think about the way they start, they generally come from accumulated mutations over time. Um, where, and those are often linked to things that um we can't control and that hopefully are true for all of us, right? Aging, right? I hope we all live to be 100 years old and have you know these wonderful lives where you're gonna have the opportunity to for exposure to carcinogens. Even we think about UV radiation. It could be environmental exposures like a job. Um, pediatric cancers, by contrast, are usually driven by, not always, but usually by disruptions in development. So because of that, the biology is really different. Um, pediatric cancers tend to have fewer mutations in them, um, but those mutations unfortunately occur in really critical pathways that control how cells grow and mature. So, what that means is that the treatments that we design for adult cancers often don't translate well to children. Um, that's the first big thing, is biology. The second is pediatric cancers are rarer. Um, each individual childhood cancer impacts a relatively small number of patients in comparison to adult cancers. And so that makes research harder to fund, harder to study, um, harder to move quickly through clinical trials where we need large numbers of patients. It also means there's less commercial incentive for industry to develop like therapies that are specific for pediatric cancer. So that's why I think philanthropy plays an outside role. And then finally, I would say children are still developing treatments that may be acceptable in adults can have lifelong consequences for children that affect their growth, their cognition, um, their heart health, fertility, and just in general their overall quality of life. So, in pediatrics, when we think about success in cancer, it we're not just thinking about survival. It's about really ensuring that children can live full, healthy lives for decades after treatment. Oh my gosh, I have one more. Um, kids respond differently to therapy. Um, children often tolerate treatment, honestly, better in the short term. But like I said, the long-term effects matter more because they have so much life ahead of them. And so that changes how clinicians think about risk, um, things like intensity and long-term follow-up. Yeah.

SPEAKER_01 11:52

Well um what are the big problems left to be solved in pediatric cancer and adult cancer? What do you think those are? Yeah.

SPEAKER_00 12:04

So I think um in I'll I guess I'll break it down into two thoughts. So for the big challenges, I I would say one of the high level is resistance. Um, and that's true both in children and adults. Um cancers can adapt to treatment over time. And so we really need and are really working hard to find better ways to predict um who will respond and who won't, and how to intervene earlier before resistance takes hold. So that's kind of an overall challenge. Um, another challenge that is true for both adults and kids is what we call tumor heterogeneity. And so what that means is that no tumors are exactly alike, full stop. Not only between patients, um, so well, I would say in the same cancer type, biology can really change really dramatically from patient to patient. Um that's why things like precision medicine, which your listeners have probably heard about, matters a lot. It's also tools like things you're interested in, like genomics and AI are becoming increasingly important in both pediatric and adult cancer. Um, the third challenge is huge. It's moving the discoveries that we make from lab and to clinic faster. I think the science that we generate is absolutely incredible. Translating it into approved treatments takes time. And in pediatrics, this is really hard because, like I mentioned before, the numbers of patients that we have are small. Trials are really complex, and then adults, we're able to scale things sometimes a little easier because um the sorry, the scale exists for adults, um, but that just becomes more complicated. Um, and then I think if you wanted to know like where things differ the most, I would say if I had to pick one thing, I would say long-term outcomes. Um, because in children, one of the biggest unsolved problems to me that we have is reducing toxicity while maintaining cure rates. Many children survive cancer but have uh lifelong side effects. And in adults, the challenge is different. We're often treating cancers that are detected later in life. Uh, they are more genetically complex and they occur alongside other health conditions. Um, and so to me, the the final thing I would mention is equity. Um, it is a major unsolved problem. Our outcomes depend too much on geography, race, yeah, socioeconomic status, and what is your access to that specialized care? And that's an area where I think folks like you uh in technology and data sharing and kind of systems-level approaches can really make a difference and help us. Yeah.

SPEAKER_01 15:12

Um, you you mentioned AI. AI is obviously in the in the water these days. Uh, talk to a little about how you think about the technology, its applicability, its future in this area.

SPEAKER_00 15:25

Yeah, about uh so AI and cancer in general is a space that we've been in for decades. Um I I could not have possibly predicted um where we would be with AI a year ago, much I mean, well, 10 years ago, much less a year ago. I mean, it's been um I would say absolutely mind-blowing. Very exciting, incredible potential. But I don't think it's magic. I also don't think it's optional. I think it is infrastructure. I think we are way past the point of asking does AI beyond, sorry, belong in cancer research and care? I think the question to me is how thoughtfully and responsibly we use it. Um I would say there's probably both in, I don't see a huge difference. I see some differences, but there's probably some just, and you can pull on any of these threads you want, but there's a couple of areas that AI is um helps us to do things better than we can do alone, uh, which is how I think about AI. The first is probably pretty obvious for your listeners, it helps us to see patterns at scale. Uh, cancer data is so complex. You know, when I was a grad student, I was still going to the library at UAB. I had $45 a month to spend to make copies of papers, and I would always overspend and get in trouble with my PI. And literally, I was taking those papers, printing them, and putting them in binders. I probably had 50 by the time I graduated of those, you know, those big honkin binders of papers from my little brain. So cancer data are incredibly complex. We have imaging, we have genomics, we have pathology, clinical outcomes. So far more than any human, much less any little Susanna in grad school, can integrate consistently. And so that's where AI can find signals really early, identify subtypes, things that we can't recognize, and helps us to predict, honestly, um, responses and resistant to treatment. The second thing is it just helps us to move so much faster, right? So it accelerates, we've seen AI accelerate discovery, uh, trial design, the decisions that we're making, um both in our own labs and as collaborators. I do think that matters a lot in pediatrics. Um, because as we talked about in pediatrics, the numbers are smaller, time is precious. And so faster learning, which can be AI-driven, means that fewer children are exposed to ineffective treatments, right? We don't want to give a kid something that's not gonna work. We don't have time to mess around. And we also don't want to give them overly toxic treatments. Um, and the last thing I think is that AI can help in cancer in general really address that equity space. Um, because if it is deployed correctly, AI has the ability to extend expertise beyond major academic centers, right? And so we can bring that decision support to a clinician in a rural geographic location or somewhere where resources are limited. Um that I love, and I think it aligns directly with the pediatric moonshot in your vision.

SPEAKER_01 18:55

Yeah. Um, here I'll let you put a crystal ball out there. It's 10 years from now. Where are we?

SPEAKER_00 19:04

Oh my gosh. Um, well, I hope you and I are not here having this conversation. I hope we've made significant progress. Um, so if I have to think about where are we in 10 years, um goodness. I think that we will be in a meaningfully different place for sure. Um, I don't think it'll be because of one breakthrough, which is what we're all looking for, right? When you read the New York Times or Time magazine, you're like, oh, they did this, and you know, and this. No, I think it's gonna be the way that everything starts to come together, and a lot of that I think will be AI supported. Um, I think we will see far more precision in treatment for sure, especially in pediatrics. Um, so instead of right now, what we do is we treat children primarily based on their tumor type and their stage. I think we will increasingly, so if I have a crystal ball and I can make it perfect, that we would be treating children based on the biology of their tumor, full stop. So, what that means in reality are more targeted treatments, um, really smart ways that we combine them and fewer kids exposed to therapies that won't help them. Um, and I'm really optimistic that we will see less toxicity as a measure of success. I think survival will no longer be a measure of success, right? So I would like to see for kids especially it's a precise treatment, it's working, and this kiddo was able to keep moving with their life, and we don't have to think about long-term side effects. And on top of that, they're surviving. I think the field is going to be much more focused on long-term outcomes rather than the short-term scenario. And that is a privilege that precision medicine should give them, where we're thinking about all those things like cognition, growth, fertility, um, heart health, right? That for kids, I don't think, I think that sacrificing their future isn't a goal, right? That that should be a way that we are able in 10 years to totally change the way we think about pediatric treatments. Um and I honestly think that in 10 years, we won't be having conversations about data integration. Um, it's going to be almost invisible, I hope. If if I'm thinking about the changes that I've seen in the past year, two years, three years, right? That AI won't feel separate, which is the way it feels now to me. And you might correct me there, but I think it feels quite separate. I think in 10 years that it'll be a part of how we do all the things I just listed for you as challenges, like how we interpret scans, how we develop clinical trials, how we guide decisions, how we help our overburdened clinicians. learn faster and across institutions. And I think it's going to close gaps in expertise. So in 10 years, I think that we will have all of that, which should lead to earlier intervention. Because we should have, because of that brilliant combination of AI and the infrastructure and brilliance that we have right now deployed in our research and practicing clinicians, we're going to have better biomarkers, we're going to have better imaging, better risk stratification, that we can intervene before disease becomes more aggressive and resistant. And, you know, honestly, I hope in 10 years that where a child lives matters a whole lot less. That advances won't be confined to these major academic centers. That, you know, community research hospitals and we have a global platform for shared learning. Yeah.

SPEAKER_01 23:01

Well all I can say is amen and I I I love your vision of the future. So for all our listeners who might be donors, might be researchers, who'd like to learn more about your work or the V Foundation, what should we tell them to do?

SPEAKER_00 23:17

Oh my goodness. Well first of all, thank you so much for the opportunity just to be here. One of the things when I talk to donors is like I I don't know how you don't know about the V Foundation. I but of course I'm completely biased. I think the the easiest place for people to learn more is to start at our website, which you can find it's easy v.org. So vforvictory.org and that's where we share in a 1,000% transparent way the science that we fund, the researchers behind it, the impact that those investments have over time. And I I do want to emphasize that everything about the V Foundation is built on trust and transparency. 100% of direct donations go straight to cancer research and our grants are selected through a very rigorous peer review process that is led by some of the top scientists and clinicians in the country. So what this means for your listeners is that if they've been impacted by cancer, you know, someone they love or someone in their community has been impacted and they want to make a difference. If they donate to the V Foundation, they can be confident their dollars are making a real difference.

SPEAKER_01 24:33

All right. Again, appreciate you taking the time today to speak with us and give me a little education on immunology and cancer.

SPEAKER_00 24:43

You are so welcome. I'm grateful. And you know if you want to hang out we can just talk for the next I don't know two, three, four years and um I'll have you all cut up. It'll be great.

SPEAKER_01 24:53

You can give me a PhD in immunology.

SPEAKER_00 24:56

Anytime. Thank you so much Timothy and thank you for where you're what you're doing. It's really through partners like yours that that we're going to change the landscape for pediatric cancer. So I appreciate you