MedBuzz: In this episode, Dr John Marshall speaks onsite at ASCO GI 2026 with his signature unscripted style. From the power of reconnecting with colleagues to the promise of emerging RAS-targeted therapies. Main Topic: In this episode of Oncology Unscripted, Dr John Marshall continues his exploration of why so many young adults are developing colorectal cancer, highlighting new research in Nature on the bacteria-produced mutagen colibactin and its link to early-onset disease and an analysis of GLP-1 receptor agonists and colon cancer mortality. Candid Conversations: Dr John Marshall sits down with Dr. Robynne Chutkan to explore the microbiome, the latest scientific insights, and the profound impact of the modern diet on human health. Together, they discuss why the healthcare community must deepen its understanding of the microbiome to more effectively treat and care for patients.
Oncology Unscripted at ASCO GI: People, Pipelines, and Precision
John Marshall, MD:
Hello, everybody, from San Francisco, California. My name is Dr. John Marshall, and you are on—maybe unwisely—Oncology Unscripted. But thanks for joining me. I love this meeting, but let's first talk about the news of 2026.
Top of the line is: we're out to get new countries. Now, I'm sort of running for mayor of Havana. I don't know if it's important that I, in fact, speak Spanish—because I don't. I speak a little bit of French. My Spanish is terrible. But maybe it won't matter, because I am who I am, and they're looking for just my kind of person to go be mayor of Havana. So, if you see that and you get a chance to vote, vote me in. I love the whole country of Cuba—it's beautiful.
Second, in today's newspaper—I couldn't believe it—this guy named Dr. Oz, you know him, he's an actual cardiologist, believe it or not. Then he became the talk show host. And then, for some reason, he's the head of CMS at this point—one of the head overseers of healthcare here in the country. And he said his position was that alcohol is good. This couldn’t have made me happier. This couldn’t have been a better holiday present, because I'm a big alcohol fan myself, and now I can feel less guilty about it. His rationale is that if you drink more, you'll be with people more, you'll be more relaxed, and the camaraderie will pay off in terms of lessening your anxiety and stress—and the world will be a happier place.
So, don’t be smart. We don't want people in our country to be intelligent or educated. Drink more. Be less educated. You'll be happier in the long run. That's the official position of our government today.
Probably the most important new news from a healthcare perspective is that the House approved an extension on the Affordable Care Act. This has been an incredible threat and uncertainty for so many of our patients. The people who depend on that health insurance could never afford cancer care without it. Having the extension of the Affordable Care Act—for them—talk about lowering your stress. Maybe better than alcohol is actually being insured.
I don’t know if you go to many meetings out there, but this one is called GI ASCO. It's always in San Francisco. It's always in this building that I'm standing in now. I have perfect attendance. I’ve been to every one since they started. You should get a special ribbon for that. I think there’s probably one down there for that.
They are a little bit more environmentally conscious—no plastic covering to this. Just a piece of paper. Totally recyclable old name badge. Way to go, ASCO, on that.
Do you go to meetings or don’t you? I come to this one for a very, very important reason. I come to this one for the people. It’s a small meeting. It’s just the GI gang, both from the industry side and the academic side. It’s a very heavy global presence that comes. I know almost everybody here, and there are only like 3,000 people here. There’s time to stop and say hello to almost everybody you know—give them a hug, share a little COVID, maybe flu, with each other—but then know that you are connected again. And this is something Zoom doesn’t do. This is something you can’t check on—somebody’s kids—over a meeting. But that’s one of the main reasons I come.
I love these people. These are people that share in our values and our motivation to try and cure cancer. We all take care of the group of cancers—GI cancers—which are the most common, most fatal cancers on our planet. We are inspired to do this. We know it’s a steep climb, and we do it together. I’m so very pleased to be a part of this community, and it’s the main reason I come.
Main reason—people. Second reason—pipelines. There’s a lot of data out there, and there are a lot of companies here that finally have new products for GI cancers. We’ll talk a little bit about that in more specific detail, but if you just look at the number of groups that are here—the number of people who’ve got innovative, new approaches—whether it’s novel immunotherapy, targeted agents, combinations of those, targeted antibodies that are delivering toxic payloads—we’re seeing waterfall plots that we haven’t seen in decades.
So, response rates, survivals, progression-free survivals that really compare favorably to our traditional chemotherapy approaches. We are on the cusp of a true revolution in the world of GI cancer.
And, surprisingly, one more—led by the world of pancreatic cancer. So, let’s talk a little bit about precision in GI oncology. The biggest breakthroughs that we are seeing at this meeting have to do with RAS targeting.
There are a bunch of RAS drugs out there now. There are some that are more out in front than others. There are some that are degraders that break down the RAS. There are some that block pan-RAS, so they hit a bunch of RAS targets. There are some that are very specific for one particular kind of RAS mutation—and they’re working.
Now, they’re not curing everybody. But we’re seeing great waterfall plots, even with single agents, in a disease that we haven’t cracked in a long, long time—and that is pancreatic cancer.
So, we are all incredibly optimistic about what we are seeing. We are anticipating approvals this year for some—maybe one or more—of these agents. We’re excited about the possibility of combining these RAS-targeted agents with things like immunotherapy or others. We are already starting to try and think about: is the pan-RAS better than an isolated targeted RAS? What are the toxicities? How are we going to manage it? Because we’re fully expecting these drugs to get approval and to get rapidly incorporated into our day-to-day management.
First, pancreas cancer. We’re seeing it in biliary cancers. We’re seeing it in stomach cancers. Where we’re not seeing it just yet is in colorectal cancer. And I would’ve predicted a long time ago that colon was going to be the easiest nut to crack. And yet, we’ve made progress. But in fact, what we’re going to see now—biliary, hepatocellular, pancreas cancer, stomach cancers—we’re going to see a lot of evolution over the next several years.
A good friend, and really a fabulous speaker, Dr. Andrew Ko from here in San Francisco—UCSF—was the discussant just an hour ago in this building, where he did a great job of setting the stage of both the excitement for the future, but also a healthy respect for what we are going to need to understand to march forward quickly but effectively for all of those patients we’re sitting across the exam room from—that need our help.
So, precision medicine is finally making its way to GI cancers—led by the RAS wave that we are seeing. So, stay tuned. You’re going to have new drugs out there. There’s going to be competition. A lot of people talking about it.
As we talked a lot about pipelines and the new drugs that were coming out, one of the common questions we get is: what's missing? What have we not been studying well enough? And I have a pretty consistent answer—and that is the microbiome.
We don’t understand the impact of those bacteria on us, on our health, on the effectiveness of drugs, etc. And until we really start digging into that science, I don’t think we’ll see that next wave of innovation. So, the answer is microbiome.
So, why do I come to GI ASCO every year? Well, you already know the number one reason—that’s people. I love them. They’re my family, and I love to catch up with them just like you do with your family around the holidays. This is my family visit for the holidays.
Second—pipelines. Understanding what’s out there today, what’s coming, and how we are going to cure patients with GI cancer. It’s going to be through these pipelines.
And then last—the latest data. And that’s around precision medicine. We are about to embark on a wave of therapies that target RAS, and you’re going to start to see cancer shrink as these new drugs come into play.
Our job, then, over the next couple of years, is to take this new understanding, this new ability to control precision medicine, and apply it to our patients—to cure more patients with GI cancers.
Thanks for joining me from San Francisco. Totally unscripted. John Marshall, Oncology Unscripted.
Microbes, Mutagens, and Mortality: CRC in a Younger Generation
John Marshall, MD: John Marshall Oncology Unscripted. A lot of good data coming out on all sorts of things. You know, I'm a colon cancer guy, so I really want to talk about two clinical trials in the colon cancer space.
One was a paper in Nature—it's actually a few months old—but, you know, I keep seeing all these young people with colon cancer, and I keep thinking: it's the microbiome. It's gotta be. And this paper actually found a version of E. coli that produces a toxin that, if you're exposed to it at a young age—say 10, 11, 12 years old—it dramatically increases your risk of getting colon cancer later.
Now, I sort of didn’t think of it as one bacterium causing one toxin causing a toxicity. I always thought it was more of a gamish—what swamp do you have? What's the nature of your rainforest, your bacteria in the colon, that's causing it? But what I'm excited about is that we're continuing to see, week after week, month after month, new data that supports a better understanding of the microbiome—one that we hope will translate into not just identifying people who are at risk for early-onset colon cancer, but, as you know, other diseases as well.
And as a related story—this comes out of Cancer Investigation—patients who are taking GLP-1 drugs had lower colon cancer death rates. So basically, they looked at colon cancer patients, and the strongest signal was in those who were obese. But if you were on a GLP-1 versus not on a GLP-1, your survival was much better on one.
So, again, how do GLP-1 drugs work? Uh, we don’t really know. But I think probably our interface with our microbiome is one of the ways they have an effect. And so it kind of feeds back to this: the healthier we can get our innards, our inner colony of bacteria—I really think it's where our soul resides—the healthier we can get that, the better our outcomes will be. Again, not just for colon cancer, but for other diseases as well.
Just some high-level stuff that you probably didn’t see in your scanning of the week’s journals.
John Marshall, Oncology Unscripted.
Rewriting the Gut Story: Diet, Microbes, and Modern Disease—Interview with Dr Robynne Chutkan
John Marshall, MD: Hey, everybody out there? John Marshall for Oncology Unscripted. I promised you my new office. It's not that great, is it? When you get old, they take you from the big office down to the small one, but I do have a view. You see, I've got the view out there—a rooftop. I can see all the air conditioners and whether they're working or not. The helipad’s just right over there. So that's gonna get exciting sometimes. I got a halo. You see my little halo in the window there? But I am sort of angelic, as you know.
But really the reason we are gathered here today is to talk about maybe my favorite topic—so much my favorite topic that my family is tired of hearing about it—and that is our microbiome. And I honestly feel like it is where our heart and our soul reside. And I, as a good Presbyterian, I actually think this is where the soul must live.
And so I am lucky enough to have, as a friend and a colleague, Dr. Robynne Chutkan, who is joining us today. She is really an expert in the microbiome, as much as any of us is an expert right now. She's leading the way in understanding this companion that we have through life, of these bacteria and other organisms that we grow and live with all our lives. And so she's nice enough to join us today to help us oncology people get a better understanding of the microbiome and its impact on our health.
So, Robynne, we have spent decades as partners in crime, and I'm so grateful to get reconnected to you. So, give the crowd a little bit of your background, and how the heck did you get interested in the microbiome?
Robynne Chutkan, MD: Well, first of all, I couldn't ask for a more wonderful kindred spirit in my obsession with the microbiome and stool and all of it. So, I knew that we were connected through more than just Georgetown and Lombardi, so thank you for that.
I am a butt doctor amongst all these very distinguished oncologists. And thank you so much for the invitation to speak at the Ruesch Symposium a few weeks ago. One of the things I really saw there was how siloed we are. I was sitting there through the talks thinking, "I went to medical school, I was chief resident—I had no idea what you guys were talking about with the pharmaceuticals." And I think some of the oncologists felt similarly when I was talking about fecal Faecalibacterium prausnitzii and short-chain fatty acids and butyric acid.
So, we're very siloed. But one thing for sure—and I appreciate your comments about the soul and so on—because when you look down at where your GI tract is located, it is smack dab in the center of your body. So there's really no question: it’s sort of the engine for everything, and all the organs—your brain, your heart, your lungs, your immune system—rely on the nutrients extracted there and the processes to function properly.
John Marshall, MD: Yeah. But you're like this highly trained gastroenterologist, and you decided—I can't remember how long ago—to sort of say, you know, this isn't really the way I think people get better. So maybe talk a little bit about that.
Robynne Chutkan, MD: Sure. Yeah. Because it was very personal. I came to Georgetown in 1997, joined the faculty as an IBD gastroenterologist, primarily focusing on IBD, which had been the focus of my fellowship at Mount Sinai. And very quickly, I realized that nobody was talking about food—including me.
Patients would come in and tell me about their diet, and I was like, “Okay, that all sounds great. What are you taking?” And this was pre-biologics—this was the late ’90s. I remember actually going to that meeting in Amsterdam for the International Organization for IBD when they were presenting the data on cA2, which became infliximab. It didn’t even have a name at the time. And so I was as skeptical as the next about the role of diet. But something happened that really stopped me in my tracks.
This was a patient—she actually worked at the hospital, a young woman—and she had relocated to New Jersey and came back after a couple of years. She worked in the radiology department, and I saw her, and I said to her, “So, what are you on? You look great.” And she said, “I’m on nothing.” And I gave my usual spiel of, “Oh, that’s like driving a car with no insurance. That’s dangerous, you know, if you have a flare-up.” And so I thought, okay, she’s feeling right, sure. Well, let me take a look at her colon.
I did her colonoscopy, and all—she had Crohn’s colitis—all the previous cobblestoning and ulceration—gone. And I was like, “You—I cannot believe this. You must be taking something. What are you doing?” And she told me about a diet she was on called the Specific Carbohydrate Diet.
John Marshall, MD: I thought it was like... because it was the Newark Costco—was just a better Costco. No, it’s a diet, actually. She was following...
Robynne Chutkan, MD: Yeah. But I'll tell you, I was really skeptical. And I wasn’t just skeptical—I was afraid for her. Because the idea that you could treat inflammatory bowel disease without medication just was so counter to what I’d been taught. I’d been taught by Dr. Janowitz, who was taught by Dr. Crohn, and came from this sort of IBD world. But I started really looking at this, and what I found—John, I'm sure it’s the same in the oncology world—is that patients were sort of in this “don’t ask, don’t tell.”
So we did a survey in my IBD clinic, and we found that 70% of the patients were using some sort of complementary or alternative technique. Now, this is 2025—it’s very different—but in 1997–1998, this was unusual. And a lot of those modalities were just things like massage, or some of them were doing herbal things. But patients were definitely looking for things. And so I started putting patients on these different diets and so on.
We ended up coming up with a modified version of the Specific Carbohydrate Diet, which is sort of a low-carb first cousin of Paleo, but adding more fiber because it seemed pretty clear that fiber was important for gut health. And we presented that data in 2014 at Digestive Disease Week, and we showed that we actually had a 79% remission rate using this diet. Now, this is 2014, so biologics had been around.
John Marshall, MD: Did anybody believe you?
Robynne Chutkan, MD: The craziest thing is that all my GI colleagues were in the exhibit hall looking at the scopes. A few foreigners—some Europeans, some folks from Asia—were interested. But there was zero interest. Crickets. It's so funny that you asked that. So it was a small study—it was 12 patients: 9 with ulcerative colitis and 3 with Crohn’s. But what we showed—not just that they felt better—we actually had endoscopic images of mucosal healing, which, as you know, is a gold standard for remission—not just “patients feel better.” And the vast majority of patients were able to get off medication completely or reduce it.
One of the things we found when we dug a little deeper with that data is that there was a clear correlation with the amount of fiber. So, the patients who just said, “Okay, I’m gonna stop eating the processed breads and pastries and cheese, and I’m gonna have bacon and eggs for breakfast, chicken for lunch, steak for dinner with two broccoli florets”—those patients really didn’t have the same result. So, there was a clear correlation with the amount of fiber people were consuming.
John Marshall, MD: Connect the dots for me. So, it is a diet modification that's changing health, and we're talking microbiome. So, I keep thinking about, you know, what is it that's actually—take us to pathways of what's that doing to our microbiome in order to sort of rebalance? I think of it as soil. I often use a rainforest, not just a pine forest.
Robynne Chutkan, MD: Absolutely—terrain. Love the—yes, the terrain. That’s exactly right. And so fiber really seems to be key. I always like to remind people it’s less about eliminating and it’s more about adding. You can overcome a hot dog or a piece of cake if you are eating enough fiber. And by fiber, I don’t mean—I always have this as a prop—this granola bar that’s been in my drawer for 10 years. Like, I don’t mean this. I should have my apple prop. But unprocessed plant fiber. Because what that does—it’s poorly digestible, indigestible fiber—the kind that gives you gas—because it’s supposed to, because it’s not there to feed you, it’s there to feed your gut microbes.
That fiber is fermented by gut bacteria in our colon by organisms like Faecalibacterium prausnitzii—ferment it, turn it into short-chain fatty acids. And short-chain fatty acids don’t just keep the lining of the gut healthy. They help to modulate the immune system to sort of keep it at that Goldilocks—not too high, not too low—level. And so, really critically important.
You can’t just take a short-chain fatty acid supplement. It doesn’t really work that way. These compounds are very labile. And so there is this direct line between fiber consumption, levels of short-chain fatty acids, and outcome.
And we saw the same thing during COVID. We saw this UMass study that looked at microbial analysis, and they found that the composition of the gut microbiome—specifically the levels of Faecalibacterium prausnitzii—were very positively associated with better outcomes with COVID, and very predictive—92% accuracy.
And what’s so interesting, John, is some of the same organisms that they found were inversely correlated with outcomes—so, Enterococcus faecalis. They saw high levels of Enterococcus faecalis were associated with poor outcomes. We see high levels of Enterococcus faecalis in the colon cancer microbiome. So, we're seeing that signature.
John Marshall, MD: So, okay. So, you've got diet affecting the rainforest or the terrain, as you say. You've got now a—I don’t know what the right words are—but a healthier balance or the right partners to go through life with. That then leads to health. So, in your case, IBD. In most of our audience's cases, you know, it’s immune responsiveness to immune therapies, to young people getting colon cancers, to, you know, primaries responding differently than metastases, for example.
So, can you sort of hypothesize connecting those dots?
Robynne Chutkan, MD: Absolutely. And I think one of the most profound ones is when we think about weight. So, we know that we can give two people the identical meal and they will extract a different amount of energy and calories from that, based on microbial composition.
Microbes can change a palate, they can change the metabolism of the foods, they can change the transit of the food through the gut. That can determine what’s absorbed. So, it is less about the meal in some ways—I mean, the meal is still important, don’t get me wrong—but your composition of microbes...
And again, you can’t just go borrow some Faecalibacterium prausnitzii from your plant-eating friend because they only stick around about half an hour or so.
So, one of the things that is very frustrating—and I’m sure you find the same thing, ’cause you talk about the CVS aisle that’s gonna fix all of this—is trying to explain to people: it’s not just some microbes; it’s the environment in which those microbes grow. And we all have plenty of healthy microbes in our gut—if we feed them correctly—that are gonna proliferate and really sort of take root, reproduce, and create shifts.
That’s much more effective than taking a store-bought probiotic. The analogy is: you take a cheetah from the plains—the Serengeti, wherever cheetahs live—and I put it in my backyard here near Rock Creek, and I feed the cheetah Cheetos... the cheetah is not gonna do very well. So, it’s not just the microbes—it’s really the environment. And you have to create that environment. And that environment seems to be a high-fiber environment.
We have data from the American Gut Project published in 2019—10,000 people from over 40 countries asking that question: what is the most important factor for a healthy microbiome? And the answer seemed to be the amount of plant diversity in the diet, with this magic number of 30. So again, it wasn’t being vegan or even vegetarian—it’s about eating more plant fiber.
John Marshall, MD: Since I first heard that magic number—30—from you just a couple of weeks ago, I’ve been counting through the week, and I’m actually pretty good. I was already pretty good, but I’m pretty close to that on most weeks.
Robynne Chutkan, MD: Fantastic.
John Marshall, MD: So, you gave me a target, and I’ve even started to share that...
Robynne Chutkan, MD: Oh, I love that.
John Marshall, MD: ...with other people out there. So I’m grateful.
John Marshall, MD: I scour the literature for papers on this subject, and mostly it's the cancer literature I'm looking for. And what I am seeing is increasingly the impact you and others like you are having on science. What was kind of fringy when you first started—to be fair—you've matured this into now being able to start to measure it and to start to be able to influence it for cancer prevention. I've seen literature around CNS disease and dementia, of course the connection to heart disease, in your world of IBD, etc. If you could wave a wand, what would you want to be able to do? What would you want to be able to measure or assess to say: you've got a good microbiome, and here's how you'll fix yours?
Robynne Chutkan, MD: Yeah, I mean, it sounds a little bit counterintuitive, but it's almost like we have to get away from the science a little bit. Because what I find is—the science—we're in this sort of retailization of medicine. It's about selling a product, whether that is a pharmaceutical product or a probiotic at CVS. And people have this idea that if I just buy the right product, I’m gonna be fine. So it really is this idea of: what sort of platform of health and wellness are we encouraging people to build?
John Marshall, MD: Well, I guess what I'm after is: is there a Chem 20 for the microbiome?
Robynne Chutkan, MD: Okay.
John Marshall, MD: Right? Uh, so how do I measure it?
Robynne Chutkan, MD: Right now—no. And let’s remember too, that after the billions of dollars and the decades spent on the Human Genome Project—how many genetic diseases did we cure? Right? So, just like the genes are just a suggestion, the microbiome isn’t magic—it’s important. We have large data sets now that show that early antibiotic use is a major risk factor for Crohn’s disease. So, I think it’s—yes—looking at a 30-year-old and what are they doing. But I think it’s really important to say: Was this person vaginally born or C-section? Were they breastfed? How many antibiotics did they get in early life? Because I think this stuff is developing decades back.
John Marshall, MD: I’ve observed that I think there are a lot of only children with early-onset colon cancer. I wonder if there is some sort of helicopter parent phenomenon.
Robynne Chutkan, MD: Oh no—that’s mine.
John Marshall, MD: We don’t have enough time to cover all of this, but I want you to talk a little bit about ultra-processed foods and what that means. But I also want you to prompt me, because in an hour I have a meeting with the dean of the medical school on another topic. But, you know, when we went to medical school, there was maybe two hours spent on microbiome. We learned it, we got the test right, and then we forgot it. Right? So, what should our curriculum be?
Talk a little bit about ultra-processed food, and then sort of give us a quick version of—if you were in charge of the curriculum right over there—what you’d do with that curriculum?
Robynne Chutkan, MD: Wonderful. So, ultra-processed foods—the NOVA classification—it’s not an acronym, it’s actually Nova, developed by Dr. Monteiro and colleagues in Brazil. Four groups. One is essentially unprocessed or minimally processed foods—so fruits, vegetables, meat, eggs, etc. Two is processed ingredients—so that’s things like oils, butter, things like that. So, group three of processed foods is sort of taking processed ingredients and adding them to an unprocessed food. Okay. But ultra-processed foods are bioengineered ingredients. So, when you start to see—I mean, the good rule of thumb is: if you start to see maltodextrin...
John Marshall, MD: Don’t we need these to feed the planet? We have people dying of starvation, and I don’t think—I personally don’t think—there’s enough money or access to, you know, the Saturday farmers’ market down in Arlington. Right? So how do we balance the need to feed the planet versus this problem?
Robynne Chutkan, MD: I mean, that’s such an important point, John. But I think there’s a lot between farmers’ market food and ultra-processed food. Because, let’s be clear—these ingredients are not added just to create the food. They’re added to increase the shelf life and the palatability—to keep us eating more and to make it so this food never goes bad. That’s not necessary—that’s commerce.
And what’s really concerning is that a lot of the people eating these foods—these are health-adjacent foods. So they’re plant milks, and gluten-free, and dairy-free, and bars. And so a lot of the people eating them think they’re really healthy. They think, “Oh, this is great—I’m eating this gluten-free thing, and I’m eating this bar, and it only has these ingredients.” But these are foods that never...
John Marshall, MD: We had a guest a couple of episodes ago, and he was the one who uncovered the fact that ultramarathon runners get more colon cancer. And one of my hypotheses is that it’s because they live on those...
Robynne Chutkan, MD: ...on the go. Absolutely. The bars and the go. Absolutely.
John Marshall, MD: So what should I tell the people down the hall?
Robynne Chutkan, MD: Well, the first thing is—it’s not either/or. We cannot be in a situation where the patients know more about this stuff than the physicians. And I think part of the problem is it’s been this like, “Oh, it’s fringe,” and “That’s functional medicine.” I’m a conventionally trained doctor. I wear a white coat. I have a prescription pad. So, we have to—right—we have to bring this into how we’re approaching patients, how we’re educating patients. Because otherwise, people are getting this from a health coach who’s selling them $3,000 worth of useless supplements and telling them not to do chemo. So, it is really an imperative that we include this, and we have to teach our residents and fellows and patients about it.
John Marshall, MD: I’m gonna let that be the last word. Dr. Robynne Chutkan—just an amazing discussion. And we could go on for maybe several episodes—maybe we should. But we have to close it there.
We know this is important. We’ve got to figure this out. And I think the better we understand the topic that you are reviewing—the microbiome—the better we will be at preventing disease and treating it once it happens. So, Dr. Robynne Chutkan, thank you very much for joining us on Oncology Unscripted.
Robynne Chutkan, MD:
Thanks for having me. Such a pleasure.
Oncology Unscripted at ASCO GI: People, Pipelines, and Precision
John Marshall, MD:
Hello, everybody, from San Francisco, California. My name is Dr. John Marshall, and you are on—maybe unwisely—Oncology Unscripted. But thanks for joining me. I love this meeting, but let's first talk about the news of 2026.
Top of the line is: we're out to get new countries. Now, I'm sort of running for mayor of Havana. I don't know if it's important that I, in fact, speak Spanish—because I don't. I speak a little bit of French. My Spanish is terrible. But maybe it won't matter, because I am who I am, and they're looking for just my kind of person to go be mayor of Havana. So, if you see that and you get a chance to vote, vote me in. I love the whole country of Cuba—it's beautiful.
Second, in today's newspaper—I couldn't believe it—this guy named Dr. Oz, you know him, he's an actual cardiologist, believe it or not. Then he became the talk show host. And then, for some reason, he's the head of CMS at this point—one of the head overseers of healthcare here in the country. And he said his position was that alcohol is good. This couldn’t have made me happier. This couldn’t have been a better holiday present, because I'm a big alcohol fan myself, and now I can feel less guilty about it. His rationale is that if you drink more, you'll be with people more, you'll be more relaxed, and the camaraderie will pay off in terms of lessening your anxiety and stress—and the world will be a happier place.
So, don’t be smart. We don't want people in our country to be intelligent or educated. Drink more. Be less educated. You'll be happier in the long run. That's the official position of our government today.
Probably the most important new news from a healthcare perspective is that the House approved an extension on the Affordable Care Act. This has been an incredible threat and uncertainty for so many of our patients. The people who depend on that health insurance could never afford cancer care without it. Having the extension of the Affordable Care Act—for them—talk about lowering your stress. Maybe better than alcohol is actually being insured.
I don’t know if you go to many meetings out there, but this one is called GI ASCO. It's always in San Francisco. It's always in this building that I'm standing in now. I have perfect attendance. I’ve been to every one since they started. You should get a special ribbon for that. I think there’s probably one down there for that.
They are a little bit more environmentally conscious—no plastic covering to this. Just a piece of paper. Totally recyclable old name badge. Way to go, ASCO, on that.
Do you go to meetings or don’t you? I come to this one for a very, very important reason. I come to this one for the people. It’s a small meeting. It’s just the GI gang, both from the industry side and the academic side. It’s a very heavy global presence that comes. I know almost everybody here, and there are only like 3,000 people here. There’s time to stop and say hello to almost everybody you know—give them a hug, share a little COVID, maybe flu, with each other—but then know that you are connected again. And this is something Zoom doesn’t do. This is something you can’t check on—somebody’s kids—over a meeting. But that’s one of the main reasons I come.
I love these people. These are people that share in our values and our motivation to try and cure cancer. We all take care of the group of cancers—GI cancers—which are the most common, most fatal cancers on our planet. We are inspired to do this. We know it’s a steep climb, and we do it together. I’m so very pleased to be a part of this community, and it’s the main reason I come.
Main reason—people. Second reason—pipelines. There’s a lot of data out there, and there are a lot of companies here that finally have new products for GI cancers. We’ll talk a little bit about that in more specific detail, but if you just look at the number of groups that are here—the number of people who’ve got innovative, new approaches—whether it’s novel immunotherapy, targeted agents, combinations of those, targeted antibodies that are delivering toxic payloads—we’re seeing waterfall plots that we haven’t seen in decades.
So, response rates, survivals, progression-free survivals that really compare favorably to our traditional chemotherapy approaches. We are on the cusp of a true revolution in the world of GI cancer.
And, surprisingly, one more—led by the world of pancreatic cancer. So, let’s talk a little bit about precision in GI oncology. The biggest breakthroughs that we are seeing at this meeting have to do with RAS targeting.
There are a bunch of RAS drugs out there now. There are some that are more out in front than others. There are some that are degraders that break down the RAS. There are some that block pan-RAS, so they hit a bunch of RAS targets. There are some that are very specific for one particular kind of RAS mutation—and they’re working.
Now, they’re not curing everybody. But we’re seeing great waterfall plots, even with single agents, in a disease that we haven’t cracked in a long, long time—and that is pancreatic cancer.
So, we are all incredibly optimistic about what we are seeing. We are anticipating approvals this year for some—maybe one or more—of these agents. We’re excited about the possibility of combining these RAS-targeted agents with things like immunotherapy or others. We are already starting to try and think about: is the pan-RAS better than an isolated targeted RAS? What are the toxicities? How are we going to manage it? Because we’re fully expecting these drugs to get approval and to get rapidly incorporated into our day-to-day management.
First, pancreas cancer. We’re seeing it in biliary cancers. We’re seeing it in stomach cancers. Where we’re not seeing it just yet is in colorectal cancer. And I would’ve predicted a long time ago that colon was going to be the easiest nut to crack. And yet, we’ve made progress. But in fact, what we’re going to see now—biliary, hepatocellular, pancreas cancer, stomach cancers—we’re going to see a lot of evolution over the next several years.
A good friend, and really a fabulous speaker, Dr. Andrew Ko from here in San Francisco—UCSF—was the discussant just an hour ago in this building, where he did a great job of setting the stage of both the excitement for the future, but also a healthy respect for what we are going to need to understand to march forward quickly but effectively for all of those patients we’re sitting across the exam room from—that need our help.
So, precision medicine is finally making its way to GI cancers—led by the RAS wave that we are seeing. So, stay tuned. You’re going to have new drugs out there. There’s going to be competition. A lot of people talking about it.
As we talked a lot about pipelines and the new drugs that were coming out, one of the common questions we get is: what's missing? What have we not been studying well enough? And I have a pretty consistent answer—and that is the microbiome.
We don’t understand the impact of those bacteria on us, on our health, on the effectiveness of drugs, etc. And until we really start digging into that science, I don’t think we’ll see that next wave of innovation. So, the answer is microbiome.
So, why do I come to GI ASCO every year? Well, you already know the number one reason—that’s people. I love them. They’re my family, and I love to catch up with them just like you do with your family around the holidays. This is my family visit for the holidays.
Second—pipelines. Understanding what’s out there today, what’s coming, and how we are going to cure patients with GI cancer. It’s going to be through these pipelines.
And then last—the latest data. And that’s around precision medicine. We are about to embark on a wave of therapies that target RAS, and you’re going to start to see cancer shrink as these new drugs come into play.
Our job, then, over the next couple of years, is to take this new understanding, this new ability to control precision medicine, and apply it to our patients—to cure more patients with GI cancers.
Thanks for joining me from San Francisco. Totally unscripted. John Marshall, Oncology Unscripted.
Microbes, Mutagens, and Mortality: CRC in a Younger Generation
John Marshall, MD: John Marshall Oncology Unscripted. A lot of good data coming out on all sorts of things. You know, I'm a colon cancer guy, so I really want to talk about two clinical trials in the colon cancer space.
One was a paper in Nature—it's actually a few months old—but, you know, I keep seeing all these young people with colon cancer, and I keep thinking: it's the microbiome. It's gotta be. And this paper actually found a version of E. coli that produces a toxin that, if you're exposed to it at a young age—say 10, 11, 12 years old—it dramatically increases your risk of getting colon cancer later.
Now, I sort of didn’t think of it as one bacterium causing one toxin causing a toxicity. I always thought it was more of a gamish—what swamp do you have? What's the nature of your rainforest, your bacteria in the colon, that's causing it? But what I'm excited about is that we're continuing to see, week after week, month after month, new data that supports a better understanding of the microbiome—one that we hope will translate into not just identifying people who are at risk for early-onset colon cancer, but, as you know, other diseases as well.
And as a related story—this comes out of Cancer Investigation—patients who are taking GLP-1 drugs had lower colon cancer death rates. So basically, they looked at colon cancer patients, and the strongest signal was in those who were obese. But if you were on a GLP-1 versus not on a GLP-1, your survival was much better on one.
So, again, how do GLP-1 drugs work? Uh, we don’t really know. But I think probably our interface with our microbiome is one of the ways they have an effect. And so it kind of feeds back to this: the healthier we can get our innards, our inner colony of bacteria—I really think it's where our soul resides—the healthier we can get that, the better our outcomes will be. Again, not just for colon cancer, but for other diseases as well.
Just some high-level stuff that you probably didn’t see in your scanning of the week’s journals.
John Marshall, Oncology Unscripted.
Rewriting the Gut Story: Diet, Microbes, and Modern Disease—Interview with Dr Robynne Chutkan
John Marshall, MD: Hey, everybody out there? John Marshall for Oncology Unscripted. I promised you my new office. It's not that great, is it? When you get old, they take you from the big office down to the small one, but I do have a view. You see, I've got the view out there—a rooftop. I can see all the air conditioners and whether they're working or not. The helipad’s just right over there. So that's gonna get exciting sometimes. I got a halo. You see my little halo in the window there? But I am sort of angelic, as you know.
But really the reason we are gathered here today is to talk about maybe my favorite topic—so much my favorite topic that my family is tired of hearing about it—and that is our microbiome. And I honestly feel like it is where our heart and our soul reside. And I, as a good Presbyterian, I actually think this is where the soul must live.
And so I am lucky enough to have, as a friend and a colleague, Dr. Robynne Chutkan, who is joining us today. She is really an expert in the microbiome, as much as any of us is an expert right now. She's leading the way in understanding this companion that we have through life, of these bacteria and other organisms that we grow and live with all our lives. And so she's nice enough to join us today to help us oncology people get a better understanding of the microbiome and its impact on our health.
So, Robynne, we have spent decades as partners in crime, and I'm so grateful to get reconnected to you. So, give the crowd a little bit of your background, and how the heck did you get interested in the microbiome?
Robynne Chutkan, MD: Well, first of all, I couldn't ask for a more wonderful kindred spirit in my obsession with the microbiome and stool and all of it. So, I knew that we were connected through more than just Georgetown and Lombardi, so thank you for that.
I am a butt doctor amongst all these very distinguished oncologists. And thank you so much for the invitation to speak at the Ruesch Symposium a few weeks ago. One of the things I really saw there was how siloed we are. I was sitting there through the talks thinking, "I went to medical school, I was chief resident—I had no idea what you guys were talking about with the pharmaceuticals." And I think some of the oncologists felt similarly when I was talking about fecal Faecalibacterium prausnitzii and short-chain fatty acids and butyric acid.
So, we're very siloed. But one thing for sure—and I appreciate your comments about the soul and so on—because when you look down at where your GI tract is located, it is smack dab in the center of your body. So there's really no question: it’s sort of the engine for everything, and all the organs—your brain, your heart, your lungs, your immune system—rely on the nutrients extracted there and the processes to function properly.
John Marshall, MD: Yeah. But you're like this highly trained gastroenterologist, and you decided—I can't remember how long ago—to sort of say, you know, this isn't really the way I think people get better. So maybe talk a little bit about that.
Robynne Chutkan, MD: Sure. Yeah. Because it was very personal. I came to Georgetown in 1997, joined the faculty as an IBD gastroenterologist, primarily focusing on IBD, which had been the focus of my fellowship at Mount Sinai. And very quickly, I realized that nobody was talking about food—including me.
Patients would come in and tell me about their diet, and I was like, “Okay, that all sounds great. What are you taking?” And this was pre-biologics—this was the late ’90s. I remember actually going to that meeting in Amsterdam for the International Organization for IBD when they were presenting the data on cA2, which became infliximab. It didn’t even have a name at the time. And so I was as skeptical as the next about the role of diet. But something happened that really stopped me in my tracks.
This was a patient—she actually worked at the hospital, a young woman—and she had relocated to New Jersey and came back after a couple of years. She worked in the radiology department, and I saw her, and I said to her, “So, what are you on? You look great.” And she said, “I’m on nothing.” And I gave my usual spiel of, “Oh, that’s like driving a car with no insurance. That’s dangerous, you know, if you have a flare-up.” And so I thought, okay, she’s feeling right, sure. Well, let me take a look at her colon.
I did her colonoscopy, and all—she had Crohn’s colitis—all the previous cobblestoning and ulceration—gone. And I was like, “You—I cannot believe this. You must be taking something. What are you doing?” And she told me about a diet she was on called the Specific Carbohydrate Diet.
John Marshall, MD: I thought it was like... because it was the Newark Costco—was just a better Costco. No, it’s a diet, actually. She was following...
Robynne Chutkan, MD: Yeah. But I'll tell you, I was really skeptical. And I wasn’t just skeptical—I was afraid for her. Because the idea that you could treat inflammatory bowel disease without medication just was so counter to what I’d been taught. I’d been taught by Dr. Janowitz, who was taught by Dr. Crohn, and came from this sort of IBD world. But I started really looking at this, and what I found—John, I'm sure it’s the same in the oncology world—is that patients were sort of in this “don’t ask, don’t tell.”
So we did a survey in my IBD clinic, and we found that 70% of the patients were using some sort of complementary or alternative technique. Now, this is 2025—it’s very different—but in 1997–1998, this was unusual. And a lot of those modalities were just things like massage, or some of them were doing herbal things. But patients were definitely looking for things. And so I started putting patients on these different diets and so on.
We ended up coming up with a modified version of the Specific Carbohydrate Diet, which is sort of a low-carb first cousin of Paleo, but adding more fiber because it seemed pretty clear that fiber was important for gut health. And we presented that data in 2014 at Digestive Disease Week, and we showed that we actually had a 79% remission rate using this diet. Now, this is 2014, so biologics had been around.
John Marshall, MD: Did anybody believe you?
Robynne Chutkan, MD: The craziest thing is that all my GI colleagues were in the exhibit hall looking at the scopes. A few foreigners—some Europeans, some folks from Asia—were interested. But there was zero interest. Crickets. It's so funny that you asked that. So it was a small study—it was 12 patients: 9 with ulcerative colitis and 3 with Crohn’s. But what we showed—not just that they felt better—we actually had endoscopic images of mucosal healing, which, as you know, is a gold standard for remission—not just “patients feel better.” And the vast majority of patients were able to get off medication completely or reduce it.
One of the things we found when we dug a little deeper with that data is that there was a clear correlation with the amount of fiber. So, the patients who just said, “Okay, I’m gonna stop eating the processed breads and pastries and cheese, and I’m gonna have bacon and eggs for breakfast, chicken for lunch, steak for dinner with two broccoli florets”—those patients really didn’t have the same result. So, there was a clear correlation with the amount of fiber people were consuming.
John Marshall, MD: Connect the dots for me. So, it is a diet modification that's changing health, and we're talking microbiome. So, I keep thinking about, you know, what is it that's actually—take us to pathways of what's that doing to our microbiome in order to sort of rebalance? I think of it as soil. I often use a rainforest, not just a pine forest.
Robynne Chutkan, MD: Absolutely—terrain. Love the—yes, the terrain. That’s exactly right. And so fiber really seems to be key. I always like to remind people it’s less about eliminating and it’s more about adding. You can overcome a hot dog or a piece of cake if you are eating enough fiber. And by fiber, I don’t mean—I always have this as a prop—this granola bar that’s been in my drawer for 10 years. Like, I don’t mean this. I should have my apple prop. But unprocessed plant fiber. Because what that does—it’s poorly digestible, indigestible fiber—the kind that gives you gas—because it’s supposed to, because it’s not there to feed you, it’s there to feed your gut microbes.
That fiber is fermented by gut bacteria in our colon by organisms like Faecalibacterium prausnitzii—ferment it, turn it into short-chain fatty acids. And short-chain fatty acids don’t just keep the lining of the gut healthy. They help to modulate the immune system to sort of keep it at that Goldilocks—not too high, not too low—level. And so, really critically important.
You can’t just take a short-chain fatty acid supplement. It doesn’t really work that way. These compounds are very labile. And so there is this direct line between fiber consumption, levels of short-chain fatty acids, and outcome.
And we saw the same thing during COVID. We saw this UMass study that looked at microbial analysis, and they found that the composition of the gut microbiome—specifically the levels of Faecalibacterium prausnitzii—were very positively associated with better outcomes with COVID, and very predictive—92% accuracy.
And what’s so interesting, John, is some of the same organisms that they found were inversely correlated with outcomes—so, Enterococcus faecalis. They saw high levels of Enterococcus faecalis were associated with poor outcomes. We see high levels of Enterococcus faecalis in the colon cancer microbiome. So, we're seeing that signature.
John Marshall, MD: So, okay. So, you've got diet affecting the rainforest or the terrain, as you say. You've got now a—I don’t know what the right words are—but a healthier balance or the right partners to go through life with. That then leads to health. So, in your case, IBD. In most of our audience's cases, you know, it’s immune responsiveness to immune therapies, to young people getting colon cancers, to, you know, primaries responding differently than metastases, for example.
So, can you sort of hypothesize connecting those dots?
Robynne Chutkan, MD: Absolutely. And I think one of the most profound ones is when we think about weight. So, we know that we can give two people the identical meal and they will extract a different amount of energy and calories from that, based on microbial composition.
Microbes can change a palate, they can change the metabolism of the foods, they can change the transit of the food through the gut. That can determine what’s absorbed. So, it is less about the meal in some ways—I mean, the meal is still important, don’t get me wrong—but your composition of microbes...
And again, you can’t just go borrow some Faecalibacterium prausnitzii from your plant-eating friend because they only stick around about half an hour or so.
So, one of the things that is very frustrating—and I’m sure you find the same thing, ’cause you talk about the CVS aisle that’s gonna fix all of this—is trying to explain to people: it’s not just some microbes; it’s the environment in which those microbes grow. And we all have plenty of healthy microbes in our gut—if we feed them correctly—that are gonna proliferate and really sort of take root, reproduce, and create shifts.
That’s much more effective than taking a store-bought probiotic. The analogy is: you take a cheetah from the plains—the Serengeti, wherever cheetahs live—and I put it in my backyard here near Rock Creek, and I feed the cheetah Cheetos... the cheetah is not gonna do very well. So, it’s not just the microbes—it’s really the environment. And you have to create that environment. And that environment seems to be a high-fiber environment.
We have data from the American Gut Project published in 2019—10,000 people from over 40 countries asking that question: what is the most important factor for a healthy microbiome? And the answer seemed to be the amount of plant diversity in the diet, with this magic number of 30. So again, it wasn’t being vegan or even vegetarian—it’s about eating more plant fiber.
John Marshall, MD: Since I first heard that magic number—30—from you just a couple of weeks ago, I’ve been counting through the week, and I’m actually pretty good. I was already pretty good, but I’m pretty close to that on most weeks.
Robynne Chutkan, MD: Fantastic.
John Marshall, MD: So, you gave me a target, and I’ve even started to share that...
Robynne Chutkan, MD: Oh, I love that.
John Marshall, MD: ...with other people out there. So I’m grateful.
John Marshall, MD: I scour the literature for papers on this subject, and mostly it's the cancer literature I'm looking for. And what I am seeing is increasingly the impact you and others like you are having on science. What was kind of fringy when you first started—to be fair—you've matured this into now being able to start to measure it and to start to be able to influence it for cancer prevention. I've seen literature around CNS disease and dementia, of course the connection to heart disease, in your world of IBD, etc. If you could wave a wand, what would you want to be able to do? What would you want to be able to measure or assess to say: you've got a good microbiome, and here's how you'll fix yours?
Robynne Chutkan, MD: Yeah, I mean, it sounds a little bit counterintuitive, but it's almost like we have to get away from the science a little bit. Because what I find is—the science—we're in this sort of retailization of medicine. It's about selling a product, whether that is a pharmaceutical product or a probiotic at CVS. And people have this idea that if I just buy the right product, I’m gonna be fine. So it really is this idea of: what sort of platform of health and wellness are we encouraging people to build?
John Marshall, MD: Well, I guess what I'm after is: is there a Chem 20 for the microbiome?
Robynne Chutkan, MD: Okay.
John Marshall, MD: Right? Uh, so how do I measure it?
Robynne Chutkan, MD: Right now—no. And let’s remember too, that after the billions of dollars and the decades spent on the Human Genome Project—how many genetic diseases did we cure? Right? So, just like the genes are just a suggestion, the microbiome isn’t magic—it’s important. We have large data sets now that show that early antibiotic use is a major risk factor for Crohn’s disease. So, I think it’s—yes—looking at a 30-year-old and what are they doing. But I think it’s really important to say: Was this person vaginally born or C-section? Were they breastfed? How many antibiotics did they get in early life? Because I think this stuff is developing decades back.
John Marshall, MD: I’ve observed that I think there are a lot of only children with early-onset colon cancer. I wonder if there is some sort of helicopter parent phenomenon.
Robynne Chutkan, MD: Oh no—that’s mine.
John Marshall, MD: We don’t have enough time to cover all of this, but I want you to talk a little bit about ultra-processed foods and what that means. But I also want you to prompt me, because in an hour I have a meeting with the dean of the medical school on another topic. But, you know, when we went to medical school, there was maybe two hours spent on microbiome. We learned it, we got the test right, and then we forgot it. Right? So, what should our curriculum be?
Talk a little bit about ultra-processed food, and then sort of give us a quick version of—if you were in charge of the curriculum right over there—what you’d do with that curriculum?
Robynne Chutkan, MD: Wonderful. So, ultra-processed foods—the NOVA classification—it’s not an acronym, it’s actually Nova, developed by Dr. Monteiro and colleagues in Brazil. Four groups. One is essentially unprocessed or minimally processed foods—so fruits, vegetables, meat, eggs, etc. Two is processed ingredients—so that’s things like oils, butter, things like that. So, group three of processed foods is sort of taking processed ingredients and adding them to an unprocessed food. Okay. But ultra-processed foods are bioengineered ingredients. So, when you start to see—I mean, the good rule of thumb is: if you start to see maltodextrin...
John Marshall, MD: Don’t we need these to feed the planet? We have people dying of starvation, and I don’t think—I personally don’t think—there’s enough money or access to, you know, the Saturday farmers’ market down in Arlington. Right? So how do we balance the need to feed the planet versus this problem?
Robynne Chutkan, MD: I mean, that’s such an important point, John. But I think there’s a lot between farmers’ market food and ultra-processed food. Because, let’s be clear—these ingredients are not added just to create the food. They’re added to increase the shelf life and the palatability—to keep us eating more and to make it so this food never goes bad. That’s not necessary—that’s commerce.
And what’s really concerning is that a lot of the people eating these foods—these are health-adjacent foods. So they’re plant milks, and gluten-free, and dairy-free, and bars. And so a lot of the people eating them think they’re really healthy. They think, “Oh, this is great—I’m eating this gluten-free thing, and I’m eating this bar, and it only has these ingredients.” But these are foods that never...
John Marshall, MD: We had a guest a couple of episodes ago, and he was the one who uncovered the fact that ultramarathon runners get more colon cancer. And one of my hypotheses is that it’s because they live on those...
Robynne Chutkan, MD: ...on the go. Absolutely. The bars and the go. Absolutely.
John Marshall, MD: So what should I tell the people down the hall?
Robynne Chutkan, MD: Well, the first thing is—it’s not either/or. We cannot be in a situation where the patients know more about this stuff than the physicians. And I think part of the problem is it’s been this like, “Oh, it’s fringe,” and “That’s functional medicine.” I’m a conventionally trained doctor. I wear a white coat. I have a prescription pad. So, we have to—right—we have to bring this into how we’re approaching patients, how we’re educating patients. Because otherwise, people are getting this from a health coach who’s selling them $3,000 worth of useless supplements and telling them not to do chemo. So, it is really an imperative that we include this, and we have to teach our residents and fellows and patients about it.
John Marshall, MD: I’m gonna let that be the last word. Dr. Robynne Chutkan—just an amazing discussion. And we could go on for maybe several episodes—maybe we should. But we have to close it there.
We know this is important. We’ve got to figure this out. And I think the better we understand the topic that you are reviewing—the microbiome—the better we will be at preventing disease and treating it once it happens. So, Dr. Robynne Chutkan, thank you very much for joining us on Oncology Unscripted.
Robynne Chutkan, MD:
Thanks for having me. Such a pleasure.