Main Topic: With the continued improvement in neoadjuvant therapies, is surgery becoming less relevant for some patients? In this episode, Dr. John Marshall explores the evolving conversation around quality of life and whether some patients with GI cancers could be spared complex surgeries when there's no evidence of disease. Is the scalpel still best when the tumor appears to be gone? Candid Conversations: From government to academia to industry, Dr Mace Rothenberg’s career has taken a unique path. Now in his third act, he's launching a groundbreaking Museum of Medicine and Biomedical Discovery to restore public trust in science—one immersive, story-driven exhibit at a time. Join Dr John Marshall as he talks with his Obi-Wan Kenobi about career evolution, the power of truth, and why understanding what we don’t know may be just as important as what we do. MedBuzz: A letter from the federal government to Harvard isn’t just bureaucratic noise—it’s a challenge to the core of academic freedom. Dr Marshall unpacks what’s in the letter, why Harvard is pushing back, and what’s at stake for science, healthcare, and the future of free thought in the United States. If academic independence falls, what follows?
No Evidence of Disease—No Need for the Knife?
John Marshall, MD: John Marshall for Oncology Unscripted. Let's talk a little science and cancer medicine. I’m gonna come at you from a little bit of a different angle. Yep. A GI cancer angle, but a little bit different.
We have long felt in order to cure GI cancers, we had to do surgery, that it was the only way to ultimately cure people. But we all know that when we do neoadjuvant something could be chemo chemoradiation. we operate. A certain sub portion of the patients have no evidence of disease in their pathology specimen, and we sort of say, we just put somebody through a big operation gastrectomy, esophagectomy, could be a Whipple, could be a rectal surgery that they actually didn't probably need or benefit from, but we had no way of determining that until we did surgery. And so, as you know as well, there's increasingly neoadjuvant therapies for a bunch of different cancers. People are having good clinical responses where after the neoadjuvant treatment, by scope or by scan, and now by new blood testing, we can't find evidence of disease. We're torn about whether we can simply watch and wait that patient and see their cancer comes back, or do we have to operate anyway.
And there's a new paper that just came out, that I used actually in last week's tumor board here at Georgetown about watchful waiting in esophageal cancer versus surgery. So basic story, neoadjuvant treatment, everybody got it. If you had a complete clinical response, you were randomized, so not done in the United States. We'd never pull it off here, were observed for clinical recurrence and not operated on unless they had a recurrence. The other half were operated on, and then they looked for survival. And believe it or not, there was no difference survival outcome. So, some of those people avoided a surgery that they didn't need in the end and no impact on the survival. Now we still need to do better because it's still pretty crummy survival in this group of patients whether you had surgery or not, but still no difference.
In rectal cancers, we are increasingly not doing surgery. I've got a 35-year-old woman who had a very good initial response, a very good response to chemoradiation, no clinical evidence of disease. Doesn't want a colon surgery and a permanent ostomy, as you might imagine, at 35 years of age. And we've been doing watchful waiting, including doing MRD testing, and so far, nine months with no evidence of disease. And I'm sure all of you have patients like that.
We are also, of course, doing this in pancreatic cancer. And the reason for obvious reasons is that it's a difficult operation. A lot of people don't want the operation. More often, it's because of where the tumor is. It might be grabbing onto a blood vessel that the surgeon doesn't really think they can get around. Or it might be that the risk of the surgery is just too great for that individual patient. So, we are doing neoadjuvant treatment. We are doing radiation, sometimes maintenance after, sometimes not, and observing. And you, like me, have had over your career some patients whose tumors never regrew and maybe just maybe got out of the need for surgery. So, this then brings up. What are the right treatments? How do you pick which patients should have surgery, which you're not. The current neoadjuvant study that's in the cooperative groups here in the United States is surgery first versus chemoradiation first, followed by surgery. Should we begin thinking about a no surgical arm in this group of patients? As our drugs are getting better, as we are learning more about targeting RAS and BRCA and the other molecular targets that we have. Will we get to a place where we can actually increasingly avoid what is fairly morbid surgery? Let's particularly think about pancreas cancer, in this regard, because remember. It's very good at sowing early seeds. It's very good at metastasizing early, and in fact, only one out of 10 is found with resectable pancreatic cancer at initial diagnosis most have already spread. So, the value of that resection, don't get me wrong, it is the way we cure people, but the relative value of that resection in the global scope of pancreatic cancer is increasingly in question. So, as we pick therapies, highest response rate, three drug combinations, 5-FU, irinotecan, liposomal irinotecan, and oxaliplatin. Highest response rate, highest survival in the books for metastatic disease. As we use regimens like that in the neoadjuvant setting, as we add to those regimens with new targeted therapies, I do think what we will see is more and more opportunities for observation in that patient population.
We held a think tank here at Georgetown back in the fall where we invited people from all over the country who were experts in this field to think about this issue and the consensus among, what I think are some of the smartest people in the world around this subject was, that yes, indeed, the improvement of chemotherapy, the advent of precision medicine, the increasing role of immunotherapy in this space will get us to a place where, in fact, we are curing more and more people with pancreatic cancer. We need to get there. We need to make the progress. We need enrollment in clinical trials, but I believe we are going to see it. I believe we're going to see progress in 2025 and 2026. So, stay tuned for more positive papers, more positive data in the world of GI cancers and in pancreatic cancer, specifically.
John Marshall for Oncology Unscripted.
MedBuzz: This Isn’t Just About Harvard—It’s About All of Us
It has indeed been a busy couple of weeks here in Washington and around our country. Specifically, the relationship between our new federal government and academic institutions. I mentioned this previously about the issues between the government and Columbia University. And as everyone knows who's listening in, the most recent confrontation is between the federal government and Harvard University. You know that recently Harvard has refused to comply with the government's demands. There's been a countersuit back from Harvard to the federal government, so I guess discussions are ongoing, Harvard did release the letter that was sent to them lead signator of this letter, I have it here in my hand, is a guy named Josh Gruenbaum, who is a government appointee by the new administration. He's the commissioner of the Federal Acquisition Service. He's co-signed by a couple of other people, I wanted to just make sure that our audience out there knows about this document can read some of the language that is in it because as a professor at an academic institution, as a member of a, a medical community out there trying to advance science, trying to be inclusive and not only who we take care of, but also who is doing the care taking. This I thought was worth bringing in short, but some high level discussion. It's a multi-page letter. You can find it online yourself first from the government. An investment, their grants, is not an entitlement, it requires that you uphold the civil rights laws, whatever those are. And they get to be the judge of whether you're holding those, upholding those civil rights laws. So, the first point they come forward with is government and leadership reforms. They want to reduce the power held by faculty, whether tenured or untenured, and administrators who are more committed to activism than scholarship. It's all it says. So how do you decide, how do you judge a faculty member's commitment to, you know, in their words, activism versus scholarship? Aren't those two in some ways connected? That was the first paragraph no longer can you hire based on race, color, religion, sex, or national origin. They're gonna contradict themselves here in a minute. No longer can you admit students based on that. No longer can you admit students, and here's the contradiction, from countries hostile to the American values, institutions inscribed in the Constitution and the Declaration of Independence, including students who are supportive of terrorism or antisemitism. So how are you gonna not do sort of biopsies of who people are, but at the same time not allow students who represent terrorism or antisemitism? They bring out this thing called viewpoint diversity. Which again seems to me to be contradictory. They were asking Harvard, not asking, telling Harvard to audit their student body, faculty and staff and leadership for viewpoint diversity. They're supposed to produce quarterly reports.
It's supposed to be by an outside group that the federal government approves. So, they're gonna have to hold up standards quarterly so that they're meeting this rule. there could be no program. with Records of antisemitism or any other bias. Pretty broad. One that's we are all struggling with is discontinuation of DEI. So, it can't be part of anything. And that students must be disciplined are not complying with all of this. So, it then puts the role of the leadership of the institution, the academic institution of overseeing and monitoring their students for compliance with all of these rules. And Mr. Gruenbaum signed that along with some others.
Can you imagine being the academic administrator who opened this letter and began to read it? You know that there are billions of dollars at stake with this relationship between just Harvard and the Federal government, and we as institutions are struggling with, do you just comply with these things? Because that's the new law of the land. Do you push back and say, that isn't the law of the land? Do you have to prove that? What really is the truth here and what do we have to do? But you can understand why this is threatening to what is truly been special about United States education, and that is the freedom of speech, the freedom of thought, the challenging of each other, and our thoughts. Acknowledging what we know, acknowledging what we don't know, whether that's around science or other fields, and investing in improving our knowledge and our understanding in that we make the world a better place for us all.
I worry about this letter a lot and I'm pretty sure you do too. For Oncology Unscripted, this is John Marshall. Let's keep our heads up. Let's keep figuring out the truth and let's make sure we share that with others. Every day makes the today a little bit better for someone nearby. That one little rock you throw in the puddle that makes the ripple, you never know how far that ripple will reach. And I'm convinced that if we keep our heads up, and, if we keep tossing those rocks in and keep making those positive ripples, that we will keep the world headed in a better direction.
John Marshall Oncology Unscripted.
Truth, Science, and the Next Big Leap: A Conversation with Dr. Mace Rothenberg
Welcome back everybody out there and wherever you are, might be video, might be audio, might be both. This is John Marshall for Oncology Unscripted. And it's been a busy week, as they say on the John Oliver Show. There's been a whole lot going on out there in the world of oncology, healthcare, relationships between the government and healthcare providers, et cetera. So, there's tons to talk about, but I want to focus right now on keeping truth and science alive. And so, I am lucky enough to know one of the world's experts. In both truth and science. Not only the creation of truth and science, but the maintenance of truth and science.
And this is a longtime friend. We won't say how long, but a longtime friend and I would actually go as far as. I refer to him as my Obi-Wan Kenobi, one of those people who had a major influence in my decision making early on in my career around GI cancers and clinical research, et cetera. And this is Dr. Mace Rothenberg. And Mace thank you first so much for being willing to be interviewed and join us on Oncology Unscripted. Welcome.
Mace Rothenberg, MD: Thank you, John. Thank you for the very kind introduction.
John Marshall, MD: I am not done because at first you started. As sort of a dumb GI oncologist, a little bit like me, but you were into drug development. You were into caring about the patient. You were into connecting your academic institution with the state of the art science, and, you were one of those folks who coached me and mentored me, as I said. But then, you surprised me, you surprised many of us, when you made a decision, back before it was something that was done regularly, of joining the industry. And I was wondering if you could just start a little bit of talking about that decision, however many years ago that was about leaving academic, medicine and cancer and going over to industry.
Tell us a little bit about that process.
Mace Rothenberg, MD: Well, it actually starts when I was training at the National Cancer Institute. So, the first part of my oncology career was actually spent in government. I did my three-year fellowship there, and then I stayed on as a junior faculty member the NCI. And then I developed some great skills, great interest in drug development, and then I got a call, one day from Dan Von Hoff at San Antonio who invited me to join academia at the university in phase one drug development. I didn't really anticipate this, but it was a call that I received, and I said, you know what, given my interests, this is the next natural step in my career. So, I moved from government to academia for seven years we were in San Antonio. The next 10 years were in Nashville at Vanderbilt. During that time, it was an opportunity to evolve as the field, as opportunities presented themselves. So, when some of the drugs we had worked with in San Antonio, like gemcitabine and irinotecan ended up having applications in GI cancer, that became my area of focus. As I developed skill in designing and running clinical trials. Had a chance then to run the phase one drug development program at Vanderbilt, and then as translational research, linking the laboratory in clinic came along, and things like SPORE grants were designed to really encourage that. I branched out into that and became co-principal investigator of the GI SPORE grant at Vanderbilt. So, I think throughout my career there was always a recognition of what I liked doing and what I was good at. But also, recognition when the new opportunity came along and I was ready for, and that happened again through a call in 2008 when I was at Vanderbilt about a new opportunity at Pfizer. Now, we've all gotten calls throughout our career from industry, and we usually say thanks, but no thanks.
John Marshall, MD: I'm too much trouble. They never call me Mace, just so you know. They're like, no, not that one.
Mace Rothenberg, MD: And, and so they were reorganizing one of the business units to be focused on oncology. They had a really great pipeline, nor known as an oncology company at the time, but they were making a real commitment. So, I decided that even though that was unanticipated, that I felt that this would be a next opportunity for me to contribute in a way I hadn't been able to before, so I decided to take that big plunge and I, I had a, a tremendous experience at Pfizer for the first 10 years, running clinical development, for the
John Marshall, MD: Let me, let me interrupt you there. Because you, because you, that, that's that decision. There are a lot of clinicians who do get that phone call.
Mace Rothenberg, MD: Yeah.
John Marshall, MD: And they think, okay, I'm gonna, this is gonna be a very different world.
Mace Rothenberg, MD: Mm-hmm.
John Marshall, MD: You're trained, you've done your whole life about seeing patients delivering care to patients. That's your world. That's your culture. Give me a little flashback on how unsettled that was, or were you excited? Was the excitement more than the unsettled part of that?
Mace Rothenberg, MD: I think with, with all big decisions, we have to think about what we're getting and what we're giving up, and I had to go through that whole thought process because what I love doing, seeing patients, being able to bring ideas from the laboratory to the clinic, being able to design the clinical trials, having the opportunity to, grand rounds to be the discussant at professional meetings like ASCO. I had to think about whether I was ready to give up those things in order to take on new responsibilities of running a large global program. Being able to prioritize the drugs within the portfolio to be able to identify where the opportunities were for us to make a big difference with the drugs we brought forward. I really had to think about that, that trade off. But as I, I've been fortunate in the big decisions I've had in my life, both personally and professionally when I sat down and thought about it, all the indicators pointed in one direction. And that was for me to move from academia to industry because I realized.
John Marshall, MD: Let me poke at one that, because when I thought about this in all sincerity over, over career. You know me, I'm a big mouth. one of my biggest worries was I was losing my ability to write my own script and was now being given a script. And you've, you've, you have, you're different in that you, you're like, you say you're my Obi-Wan. You have this sort of good, deep rudder. You're centered; you're focused. So, when you had to take on a company script, if you will. Did you feel that way? Or coach me a little bit on that experience.
Mace Rothenberg, MD: You know, I didn't feel that way. I felt that they were recruiting me because they needed my critical thinking abilities, my ability to be able to, to take the information that was available to sift through it, to analyze it, and then to be able to come up with a recommendation.
John Marshall, MD: Let me go, let me go a little deeper then. So, what, what if I was younger, you got a really cool high-level position too,
Mace Rothenberg, MD: Mm-hmm. Mm-hmm.
John Marshall, MD: have some junior people listening to us today. So, what if your job is at a lower level, you're given one drug, you're to develop that one drug or whatnot. It is a very narrow focus that you now have. I thought of that as both a positive and a negative as an individual, as you've seen other folks come along. And as the culture has shifted that more and more, industry is hiring physicians, do you see that as a, a distinction or not?
Mace Rothenberg, MD: Even though you may be assigned to one project or one drug, you are not defined by that one drug. Your career does not depend on that one drug. In fact, when there were failures in our portfolio during my tenure at Pfizer, no one lost their position because the drug they're working on failed. In fact, we needed to be very honest and recognize what the drugs we thought they could do and what they actually could deliver and then be able to re-deploy those assets to areas where they're more likely to be successful and to help patients. And so, what I would tell people in my team is that your skills are too valuable to spend it on toiling on a drug that's never gonna help a patient. We need to redeploy you in drugs that will help patients. And that's, that's the way we're able to operate. So, I don't want anyone to ever feel that they're defined by the success or failure of one drug. Your career is more than that. You are more than that.
John Marshall, MD: So, you had a remarkable first career developing new medicines that have had an impact on patients around the world. You had a remarkable second career where you then were able to deploy this and develop even more pipeline, with your commitment to Pfizer. And now, I recently figured out that you got a third career cooking now as someone who's going to be a keeper of the truth or helping to provide others with the truth and this concept of building an essentially a science or medical or biotech museum.
And our audience would really love to hear about this. So, I'm gonna shut up and you tell us what your newest career is all about.
Mace Rothenberg, MD: So, something I'd been thinking about for, for a while even though there were some tremendous advances in science and medicine in the course of our careers and our lives, all the places and venues that you go and see these things. Museums of medicine, for instance, were very static. Basically, displaying artifacts behind glass that you read about. And we know how exciting and wonderful and wondrous and joyful medical research can be. Scientific discoveries can enable us to gain insight into health and disease and from those insights come new medicines and interventions that change our lives and change the world. Yet there was no place that captured that excitement, that wonder. So, I began talking to people about it. And for several years people said, interesting idea. Good luck. It was only in late 2021 that in the conversation I was having with Larry Marett over dinner, he was at that time, Dean of Basic Sciences at Vanderbilt. Someone I had known for 25 years whose response was different.
After I told him about this idea, he looked at me and said, great idea. Let's do it. So that's also something that's been critical in my career is having people who believed in me, believed in the idea and were willing to help along the way. So, this was one of those moments, and thanks to his belief and the resources, he was able to garner the, the people he was able to bring to the table. We took this nebulous idea and began to refine it to identify what the problem was we were trying to address. What the vision was, what the mission would be, because we needed something that could be able to convey this not just to other professionals, but to the general public whose belief and trust in science and medicine have been eroding for the last five years. Despite all the things that we've done, all the great renowned researchers and scientists and government officials who speak to the public. That has not gained the trust and respect and traction that we should have. So, I began thinking about other ways we could do this, and out of that, sprung the Museum of Medicine and biomedical discovery.
John Marshall, MD: Do you think that the trust imbalance, right as you, as you allude to, is that we are learning more and more about how things work? and the public is increasingly skeptical about what, what we know and what we don't know. True.
Mace Rothenberg, MD: Yeah.
John Marshall, MD: do you think that's because it's more complicated? Do you think there's counter voices that are being heard more strongly? The idea around this museum, around this information, resource is to try and level that field a little bit. And when we first talked. I was thinking about how I learned. I learned once I can see it in my head, once I can create a visual, once I saw in my head DNA spinning around, or once I saw a protein docking, then I got it and, and I could under, I could read it and see it at the same time and believe it. Whereas many people don't have that skillset or never really don't learn that way, for example. So, give me a sense from your angle. The problem of why the distrust, and why you think this strategy will help bridge that.
Mace Rothenberg, MD: I think for far too long we as professionals have spoken to the public as if there were other scientists and researchers and medical professionals, and that they were purely fact-based. That's what we like to think of ourselves, we're evidence-based. But the public. Isn't wired that way. They take the facts that we provide and put them into context of their own lives, their community, their political affiliate affiliations. lots of different factors that come into how much, how they process that information. And we've not been responsive to that. And one thing that I've known about myself is that I don't learn just when I'm presented with a list of facts. That's why I really wasn't very good medical student for the first two years where it was just rote memorization. It was only in the second two years of my training when we actually got into the clinic and got into the hospital and I could see patients who had those symptoms, and those symptoms put together into diagnosis that it began to stick with me. And so I think the same approach is needed in trying to convey the progress we've made in science and medicine by telling stories that engage the visitors and to do it in a way that uses 21st century technology, like immersive interactive platforms, to be able to take them on the arc from that scientific discovery in the laboratory all the way through how a medicine or intervention was developed and the impact that that's had on, on, on people.
John Marshall, MD: I really love you.
Mace Rothenberg, MD: that'll
John Marshall, MD: You know, I get you. I'd really love your opinion on, on, on this or reflect on this. We, in healthcare and science in general are quite proud of what we know, but it's only as we get older, you and me are actually comfortable in saying what we don't know. And so, I wonder on some level is that if, if we, if we came clean on what we don't know. Better. Would it also help legitimize those things? We do know, and I, I was thinking about, you know, putting together exhibits. Obviously, you're gonna put together things of what we know, of what we've learned of new, of, of knowledge, but isn't it also equally important to understand the list of things that we are curious about, or we don't know.
Mace Rothenberg, MD: Yeah. that is perfectly described from the perspective of a researcher. But when you, you, you take away that and look at it from a lay person's perspective, they want to know what is it, what's true? What should I do? And, and I'll do it, because they trust you. The problem is what they, what, what's often not conveyed is that you know this to be true as of today. Yet because of science and research, we're gonna know more tomorrow. And the next day. And the next day. And some of the things that we believe to be true today, may be proven to be not as true as we think they are tomorrow, or next year, or in five years. That's the nature of discovery. Whether you're talking about medicine or space exploration, we are constantly learning more, and that's something that we haven't conveyed to the public very well.
Think about the COVID pandemic when we talked about social distancing, cleaning services because we are concerned that COVID could be spread in that way and how later on we said, no, actually it's more spread through aerosol root. And people were confused. They said, wait a second. You told me one thing yesterday, another thing today, what, what makes me certain that if I do this today, it won't be reversed tomorrow? So, we didn't really get through to the lay public that this is, this is the nature we're giving the best advice we have based on the information we have today.
John Marshall, MD: I want you to, I want to spend the closing moments that we have together of telling us where are you with this idea? I know you're pretty far along. How can we as a scientific and medical community help accelerate your progress? Obviously, very important project that could benefit all of us, all of humanity.
Tell us where you are. How can we help you?
Mace Rothenberg, MD: Well, we've been in existence for about two and a half years. We have had receptions in major cities. We have launched a website. We have engaged with museum design and planning firms, and we actually have a three-phase plan for development. So, the first phase is going to be creation of an exhibit. In fact, the topic for the first exhibit is gonna be cancer, and it’s tentatively titled Cancer, from Despair to Discovery to Triumph. And it'll actually take visitors on a journey, not just throwing facts at them, but by drawing them into the story. So just as, as an example, when a visitor enters the exhibit, they're gonna be met by people, people of all ages and ethnicities and backgrounds, talking about what their lives are like as a truck driver, as a third grader, as a business person. And then, their lives were changed by one word, cancer. That brings people into the story, putting a human face on this, not just throwing facts at people. And then going into the exhibit, what is cancer? And the, the 12 essential characteristics that Hanahan and Weinberg described, which will allow people to explore and delve into that deeply. And in fact, understand why cancer detection is better because the cancers haven't developed all those characteristics yet, so they're caught early stages when they're treatable and curable. what? What we do to help the body fight cancer beyond just chemotherapy and radiation and surgery, but things like immunotherapy, cellular therapies, protein degradation, and again, imagine being able not just to read about what a CAR T cell does, but to actually climb in one. See how it's created. See how it's trained to recognize the cancer and travel along through the bloodstream. To see it find and kill that cancer cell. Those are the kinds of immersive experiences that that aren't available elsewhere and that we need to tell in order to engage people. Another thing is that we're not going to be trying to convince people of anything. What we're gonna try and do is open up what's currently a black box to the public to say, this is how science is, is performed. This is how discoveries are made, and this is how it's translated. We're gonna be very open about the fact that we're not always right. We make mistakes. There's a role of serendipity. There's the ethical aspect as well where we have, we have made mistakes over time. What were those mistakes? How were they detected and what steps were taken to correct them and prevent them from happening in the future? So, these are the things we plan for the museum, and I'm just, I can't wait. We're able to bring that forward and show people what we can do and tell these stories.
John Marshall, MD: I know you didn't ask, but I just can't resist. I think the CAR T thing needs to be bumper cars. You actually get in one and you bump into other cells, if you will, and you, you.
Mace Rothenberg, MD: right.
John Marshall, MD: There you go. I, you, you can just have that one for free. You, you,
Mace Rothenberg, MD: That would be great.
John Marshall, MD: We need to help you do this, and we'll certainly help promote the activity. We know it's both a fundraising effort, but also an awareness effort, that's out there to make this be a reality. And I,
Mace Rothenberg, MD: Yeah.
John Marshall, MD: know that all of our listeners hear the need and hear how your strategy and your project and all your past successes are funneling into a new one that'll be left for generations to come.
So, Dr. Mace Rothenberg, I cannot thank you enough for taking the time today to join us, and we really, really appreciate your time and we only wish you success in your third career as a museum developer. Mace. Thank you.
Mace Rothenberg, MD: Thank Really appreciate.
John Marshall, MD:
I cannot thank Dr. Mace Rothenberg enough. First at NCI, San Antonio, Vanderbilt, and Pfizer now in the next phase of his career is going to build out a museum that's gonna change the lives of all of us in our understanding of science and help keep truth alive. So, Mace, again, thank you very much for joining us.
No Evidence of Disease—No Need for the Knife?
John Marshall, MD: John Marshall for Oncology Unscripted. Let's talk a little science and cancer medicine. I’m gonna come at you from a little bit of a different angle. Yep. A GI cancer angle, but a little bit different.
We have long felt in order to cure GI cancers, we had to do surgery, that it was the only way to ultimately cure people. But we all know that when we do neoadjuvant something could be chemo chemoradiation. we operate. A certain sub portion of the patients have no evidence of disease in their pathology specimen, and we sort of say, we just put somebody through a big operation gastrectomy, esophagectomy, could be a Whipple, could be a rectal surgery that they actually didn't probably need or benefit from, but we had no way of determining that until we did surgery. And so, as you know as well, there's increasingly neoadjuvant therapies for a bunch of different cancers. People are having good clinical responses where after the neoadjuvant treatment, by scope or by scan, and now by new blood testing, we can't find evidence of disease. We're torn about whether we can simply watch and wait that patient and see their cancer comes back, or do we have to operate anyway.
And there's a new paper that just came out, that I used actually in last week's tumor board here at Georgetown about watchful waiting in esophageal cancer versus surgery. So basic story, neoadjuvant treatment, everybody got it. If you had a complete clinical response, you were randomized, so not done in the United States. We'd never pull it off here, were observed for clinical recurrence and not operated on unless they had a recurrence. The other half were operated on, and then they looked for survival. And believe it or not, there was no difference survival outcome. So, some of those people avoided a surgery that they didn't need in the end and no impact on the survival. Now we still need to do better because it's still pretty crummy survival in this group of patients whether you had surgery or not, but still no difference.
In rectal cancers, we are increasingly not doing surgery. I've got a 35-year-old woman who had a very good initial response, a very good response to chemoradiation, no clinical evidence of disease. Doesn't want a colon surgery and a permanent ostomy, as you might imagine, at 35 years of age. And we've been doing watchful waiting, including doing MRD testing, and so far, nine months with no evidence of disease. And I'm sure all of you have patients like that.
We are also, of course, doing this in pancreatic cancer. And the reason for obvious reasons is that it's a difficult operation. A lot of people don't want the operation. More often, it's because of where the tumor is. It might be grabbing onto a blood vessel that the surgeon doesn't really think they can get around. Or it might be that the risk of the surgery is just too great for that individual patient. So, we are doing neoadjuvant treatment. We are doing radiation, sometimes maintenance after, sometimes not, and observing. And you, like me, have had over your career some patients whose tumors never regrew and maybe just maybe got out of the need for surgery. So, this then brings up. What are the right treatments? How do you pick which patients should have surgery, which you're not. The current neoadjuvant study that's in the cooperative groups here in the United States is surgery first versus chemoradiation first, followed by surgery. Should we begin thinking about a no surgical arm in this group of patients? As our drugs are getting better, as we are learning more about targeting RAS and BRCA and the other molecular targets that we have. Will we get to a place where we can actually increasingly avoid what is fairly morbid surgery? Let's particularly think about pancreas cancer, in this regard, because remember. It's very good at sowing early seeds. It's very good at metastasizing early, and in fact, only one out of 10 is found with resectable pancreatic cancer at initial diagnosis most have already spread. So, the value of that resection, don't get me wrong, it is the way we cure people, but the relative value of that resection in the global scope of pancreatic cancer is increasingly in question. So, as we pick therapies, highest response rate, three drug combinations, 5-FU, irinotecan, liposomal irinotecan, and oxaliplatin. Highest response rate, highest survival in the books for metastatic disease. As we use regimens like that in the neoadjuvant setting, as we add to those regimens with new targeted therapies, I do think what we will see is more and more opportunities for observation in that patient population.
We held a think tank here at Georgetown back in the fall where we invited people from all over the country who were experts in this field to think about this issue and the consensus among, what I think are some of the smartest people in the world around this subject was, that yes, indeed, the improvement of chemotherapy, the advent of precision medicine, the increasing role of immunotherapy in this space will get us to a place where, in fact, we are curing more and more people with pancreatic cancer. We need to get there. We need to make the progress. We need enrollment in clinical trials, but I believe we are going to see it. I believe we're going to see progress in 2025 and 2026. So, stay tuned for more positive papers, more positive data in the world of GI cancers and in pancreatic cancer, specifically.
John Marshall for Oncology Unscripted.
MedBuzz: This Isn’t Just About Harvard—It’s About All of Us
It has indeed been a busy couple of weeks here in Washington and around our country. Specifically, the relationship between our new federal government and academic institutions. I mentioned this previously about the issues between the government and Columbia University. And as everyone knows who's listening in, the most recent confrontation is between the federal government and Harvard University. You know that recently Harvard has refused to comply with the government's demands. There's been a countersuit back from Harvard to the federal government, so I guess discussions are ongoing, Harvard did release the letter that was sent to them lead signator of this letter, I have it here in my hand, is a guy named Josh Gruenbaum, who is a government appointee by the new administration. He's the commissioner of the Federal Acquisition Service. He's co-signed by a couple of other people, I wanted to just make sure that our audience out there knows about this document can read some of the language that is in it because as a professor at an academic institution, as a member of a, a medical community out there trying to advance science, trying to be inclusive and not only who we take care of, but also who is doing the care taking. This I thought was worth bringing in short, but some high level discussion. It's a multi-page letter. You can find it online yourself first from the government. An investment, their grants, is not an entitlement, it requires that you uphold the civil rights laws, whatever those are. And they get to be the judge of whether you're holding those, upholding those civil rights laws. So, the first point they come forward with is government and leadership reforms. They want to reduce the power held by faculty, whether tenured or untenured, and administrators who are more committed to activism than scholarship. It's all it says. So how do you decide, how do you judge a faculty member's commitment to, you know, in their words, activism versus scholarship? Aren't those two in some ways connected? That was the first paragraph no longer can you hire based on race, color, religion, sex, or national origin. They're gonna contradict themselves here in a minute. No longer can you admit students based on that. No longer can you admit students, and here's the contradiction, from countries hostile to the American values, institutions inscribed in the Constitution and the Declaration of Independence, including students who are supportive of terrorism or antisemitism. So how are you gonna not do sort of biopsies of who people are, but at the same time not allow students who represent terrorism or antisemitism? They bring out this thing called viewpoint diversity. Which again seems to me to be contradictory. They were asking Harvard, not asking, telling Harvard to audit their student body, faculty and staff and leadership for viewpoint diversity. They're supposed to produce quarterly reports.
It's supposed to be by an outside group that the federal government approves. So, they're gonna have to hold up standards quarterly so that they're meeting this rule. there could be no program. with Records of antisemitism or any other bias. Pretty broad. One that's we are all struggling with is discontinuation of DEI. So, it can't be part of anything. And that students must be disciplined are not complying with all of this. So, it then puts the role of the leadership of the institution, the academic institution of overseeing and monitoring their students for compliance with all of these rules. And Mr. Gruenbaum signed that along with some others.
Can you imagine being the academic administrator who opened this letter and began to read it? You know that there are billions of dollars at stake with this relationship between just Harvard and the Federal government, and we as institutions are struggling with, do you just comply with these things? Because that's the new law of the land. Do you push back and say, that isn't the law of the land? Do you have to prove that? What really is the truth here and what do we have to do? But you can understand why this is threatening to what is truly been special about United States education, and that is the freedom of speech, the freedom of thought, the challenging of each other, and our thoughts. Acknowledging what we know, acknowledging what we don't know, whether that's around science or other fields, and investing in improving our knowledge and our understanding in that we make the world a better place for us all.
I worry about this letter a lot and I'm pretty sure you do too. For Oncology Unscripted, this is John Marshall. Let's keep our heads up. Let's keep figuring out the truth and let's make sure we share that with others. Every day makes the today a little bit better for someone nearby. That one little rock you throw in the puddle that makes the ripple, you never know how far that ripple will reach. And I'm convinced that if we keep our heads up, and, if we keep tossing those rocks in and keep making those positive ripples, that we will keep the world headed in a better direction.
John Marshall Oncology Unscripted.
Truth, Science, and the Next Big Leap: A Conversation with Dr. Mace Rothenberg
Welcome back everybody out there and wherever you are, might be video, might be audio, might be both. This is John Marshall for Oncology Unscripted. And it's been a busy week, as they say on the John Oliver Show. There's been a whole lot going on out there in the world of oncology, healthcare, relationships between the government and healthcare providers, et cetera. So, there's tons to talk about, but I want to focus right now on keeping truth and science alive. And so, I am lucky enough to know one of the world's experts. In both truth and science. Not only the creation of truth and science, but the maintenance of truth and science.
And this is a longtime friend. We won't say how long, but a longtime friend and I would actually go as far as. I refer to him as my Obi-Wan Kenobi, one of those people who had a major influence in my decision making early on in my career around GI cancers and clinical research, et cetera. And this is Dr. Mace Rothenberg. And Mace thank you first so much for being willing to be interviewed and join us on Oncology Unscripted. Welcome.
Mace Rothenberg, MD: Thank you, John. Thank you for the very kind introduction.
John Marshall, MD: I am not done because at first you started. As sort of a dumb GI oncologist, a little bit like me, but you were into drug development. You were into caring about the patient. You were into connecting your academic institution with the state of the art science, and, you were one of those folks who coached me and mentored me, as I said. But then, you surprised me, you surprised many of us, when you made a decision, back before it was something that was done regularly, of joining the industry. And I was wondering if you could just start a little bit of talking about that decision, however many years ago that was about leaving academic, medicine and cancer and going over to industry.
Tell us a little bit about that process.
Mace Rothenberg, MD: Well, it actually starts when I was training at the National Cancer Institute. So, the first part of my oncology career was actually spent in government. I did my three-year fellowship there, and then I stayed on as a junior faculty member the NCI. And then I developed some great skills, great interest in drug development, and then I got a call, one day from Dan Von Hoff at San Antonio who invited me to join academia at the university in phase one drug development. I didn't really anticipate this, but it was a call that I received, and I said, you know what, given my interests, this is the next natural step in my career. So, I moved from government to academia for seven years we were in San Antonio. The next 10 years were in Nashville at Vanderbilt. During that time, it was an opportunity to evolve as the field, as opportunities presented themselves. So, when some of the drugs we had worked with in San Antonio, like gemcitabine and irinotecan ended up having applications in GI cancer, that became my area of focus. As I developed skill in designing and running clinical trials. Had a chance then to run the phase one drug development program at Vanderbilt, and then as translational research, linking the laboratory in clinic came along, and things like SPORE grants were designed to really encourage that. I branched out into that and became co-principal investigator of the GI SPORE grant at Vanderbilt. So, I think throughout my career there was always a recognition of what I liked doing and what I was good at. But also, recognition when the new opportunity came along and I was ready for, and that happened again through a call in 2008 when I was at Vanderbilt about a new opportunity at Pfizer. Now, we've all gotten calls throughout our career from industry, and we usually say thanks, but no thanks.
John Marshall, MD: I'm too much trouble. They never call me Mace, just so you know. They're like, no, not that one.
Mace Rothenberg, MD: And, and so they were reorganizing one of the business units to be focused on oncology. They had a really great pipeline, nor known as an oncology company at the time, but they were making a real commitment. So, I decided that even though that was unanticipated, that I felt that this would be a next opportunity for me to contribute in a way I hadn't been able to before, so I decided to take that big plunge and I, I had a, a tremendous experience at Pfizer for the first 10 years, running clinical development, for the
John Marshall, MD: Let me, let me interrupt you there. Because you, because you, that, that's that decision. There are a lot of clinicians who do get that phone call.
Mace Rothenberg, MD: Yeah.
John Marshall, MD: And they think, okay, I'm gonna, this is gonna be a very different world.
Mace Rothenberg, MD: Mm-hmm.
John Marshall, MD: You're trained, you've done your whole life about seeing patients delivering care to patients. That's your world. That's your culture. Give me a little flashback on how unsettled that was, or were you excited? Was the excitement more than the unsettled part of that?
Mace Rothenberg, MD: I think with, with all big decisions, we have to think about what we're getting and what we're giving up, and I had to go through that whole thought process because what I love doing, seeing patients, being able to bring ideas from the laboratory to the clinic, being able to design the clinical trials, having the opportunity to, grand rounds to be the discussant at professional meetings like ASCO. I had to think about whether I was ready to give up those things in order to take on new responsibilities of running a large global program. Being able to prioritize the drugs within the portfolio to be able to identify where the opportunities were for us to make a big difference with the drugs we brought forward. I really had to think about that, that trade off. But as I, I've been fortunate in the big decisions I've had in my life, both personally and professionally when I sat down and thought about it, all the indicators pointed in one direction. And that was for me to move from academia to industry because I realized.
John Marshall, MD: Let me poke at one that, because when I thought about this in all sincerity over, over career. You know me, I'm a big mouth. one of my biggest worries was I was losing my ability to write my own script and was now being given a script. And you've, you've, you have, you're different in that you, you're like, you say you're my Obi-Wan. You have this sort of good, deep rudder. You're centered; you're focused. So, when you had to take on a company script, if you will. Did you feel that way? Or coach me a little bit on that experience.
Mace Rothenberg, MD: You know, I didn't feel that way. I felt that they were recruiting me because they needed my critical thinking abilities, my ability to be able to, to take the information that was available to sift through it, to analyze it, and then to be able to come up with a recommendation.
John Marshall, MD: Let me go, let me go a little deeper then. So, what, what if I was younger, you got a really cool high-level position too,
Mace Rothenberg, MD: Mm-hmm. Mm-hmm.
John Marshall, MD: have some junior people listening to us today. So, what if your job is at a lower level, you're given one drug, you're to develop that one drug or whatnot. It is a very narrow focus that you now have. I thought of that as both a positive and a negative as an individual, as you've seen other folks come along. And as the culture has shifted that more and more, industry is hiring physicians, do you see that as a, a distinction or not?
Mace Rothenberg, MD: Even though you may be assigned to one project or one drug, you are not defined by that one drug. Your career does not depend on that one drug. In fact, when there were failures in our portfolio during my tenure at Pfizer, no one lost their position because the drug they're working on failed. In fact, we needed to be very honest and recognize what the drugs we thought they could do and what they actually could deliver and then be able to re-deploy those assets to areas where they're more likely to be successful and to help patients. And so, what I would tell people in my team is that your skills are too valuable to spend it on toiling on a drug that's never gonna help a patient. We need to redeploy you in drugs that will help patients. And that's, that's the way we're able to operate. So, I don't want anyone to ever feel that they're defined by the success or failure of one drug. Your career is more than that. You are more than that.
John Marshall, MD: So, you had a remarkable first career developing new medicines that have had an impact on patients around the world. You had a remarkable second career where you then were able to deploy this and develop even more pipeline, with your commitment to Pfizer. And now, I recently figured out that you got a third career cooking now as someone who's going to be a keeper of the truth or helping to provide others with the truth and this concept of building an essentially a science or medical or biotech museum.
And our audience would really love to hear about this. So, I'm gonna shut up and you tell us what your newest career is all about.
Mace Rothenberg, MD: So, something I'd been thinking about for, for a while even though there were some tremendous advances in science and medicine in the course of our careers and our lives, all the places and venues that you go and see these things. Museums of medicine, for instance, were very static. Basically, displaying artifacts behind glass that you read about. And we know how exciting and wonderful and wondrous and joyful medical research can be. Scientific discoveries can enable us to gain insight into health and disease and from those insights come new medicines and interventions that change our lives and change the world. Yet there was no place that captured that excitement, that wonder. So, I began talking to people about it. And for several years people said, interesting idea. Good luck. It was only in late 2021 that in the conversation I was having with Larry Marett over dinner, he was at that time, Dean of Basic Sciences at Vanderbilt. Someone I had known for 25 years whose response was different.
After I told him about this idea, he looked at me and said, great idea. Let's do it. So that's also something that's been critical in my career is having people who believed in me, believed in the idea and were willing to help along the way. So, this was one of those moments, and thanks to his belief and the resources, he was able to garner the, the people he was able to bring to the table. We took this nebulous idea and began to refine it to identify what the problem was we were trying to address. What the vision was, what the mission would be, because we needed something that could be able to convey this not just to other professionals, but to the general public whose belief and trust in science and medicine have been eroding for the last five years. Despite all the things that we've done, all the great renowned researchers and scientists and government officials who speak to the public. That has not gained the trust and respect and traction that we should have. So, I began thinking about other ways we could do this, and out of that, sprung the Museum of Medicine and biomedical discovery.
John Marshall, MD: Do you think that the trust imbalance, right as you, as you allude to, is that we are learning more and more about how things work? and the public is increasingly skeptical about what, what we know and what we don't know. True.
Mace Rothenberg, MD: Yeah.
John Marshall, MD: do you think that's because it's more complicated? Do you think there's counter voices that are being heard more strongly? The idea around this museum, around this information, resource is to try and level that field a little bit. And when we first talked. I was thinking about how I learned. I learned once I can see it in my head, once I can create a visual, once I saw in my head DNA spinning around, or once I saw a protein docking, then I got it and, and I could under, I could read it and see it at the same time and believe it. Whereas many people don't have that skillset or never really don't learn that way, for example. So, give me a sense from your angle. The problem of why the distrust, and why you think this strategy will help bridge that.
Mace Rothenberg, MD: I think for far too long we as professionals have spoken to the public as if there were other scientists and researchers and medical professionals, and that they were purely fact-based. That's what we like to think of ourselves, we're evidence-based. But the public. Isn't wired that way. They take the facts that we provide and put them into context of their own lives, their community, their political affiliate affiliations. lots of different factors that come into how much, how they process that information. And we've not been responsive to that. And one thing that I've known about myself is that I don't learn just when I'm presented with a list of facts. That's why I really wasn't very good medical student for the first two years where it was just rote memorization. It was only in the second two years of my training when we actually got into the clinic and got into the hospital and I could see patients who had those symptoms, and those symptoms put together into diagnosis that it began to stick with me. And so I think the same approach is needed in trying to convey the progress we've made in science and medicine by telling stories that engage the visitors and to do it in a way that uses 21st century technology, like immersive interactive platforms, to be able to take them on the arc from that scientific discovery in the laboratory all the way through how a medicine or intervention was developed and the impact that that's had on, on, on people.
John Marshall, MD: I really love you.
Mace Rothenberg, MD: that'll
John Marshall, MD: You know, I get you. I'd really love your opinion on, on, on this or reflect on this. We, in healthcare and science in general are quite proud of what we know, but it's only as we get older, you and me are actually comfortable in saying what we don't know. And so, I wonder on some level is that if, if we, if we came clean on what we don't know. Better. Would it also help legitimize those things? We do know, and I, I was thinking about, you know, putting together exhibits. Obviously, you're gonna put together things of what we know, of what we've learned of new, of, of knowledge, but isn't it also equally important to understand the list of things that we are curious about, or we don't know.
Mace Rothenberg, MD: Yeah. that is perfectly described from the perspective of a researcher. But when you, you, you take away that and look at it from a lay person's perspective, they want to know what is it, what's true? What should I do? And, and I'll do it, because they trust you. The problem is what they, what, what's often not conveyed is that you know this to be true as of today. Yet because of science and research, we're gonna know more tomorrow. And the next day. And the next day. And some of the things that we believe to be true today, may be proven to be not as true as we think they are tomorrow, or next year, or in five years. That's the nature of discovery. Whether you're talking about medicine or space exploration, we are constantly learning more, and that's something that we haven't conveyed to the public very well.
Think about the COVID pandemic when we talked about social distancing, cleaning services because we are concerned that COVID could be spread in that way and how later on we said, no, actually it's more spread through aerosol root. And people were confused. They said, wait a second. You told me one thing yesterday, another thing today, what, what makes me certain that if I do this today, it won't be reversed tomorrow? So, we didn't really get through to the lay public that this is, this is the nature we're giving the best advice we have based on the information we have today.
John Marshall, MD: I want you to, I want to spend the closing moments that we have together of telling us where are you with this idea? I know you're pretty far along. How can we as a scientific and medical community help accelerate your progress? Obviously, very important project that could benefit all of us, all of humanity.
Tell us where you are. How can we help you?
Mace Rothenberg, MD: Well, we've been in existence for about two and a half years. We have had receptions in major cities. We have launched a website. We have engaged with museum design and planning firms, and we actually have a three-phase plan for development. So, the first phase is going to be creation of an exhibit. In fact, the topic for the first exhibit is gonna be cancer, and it’s tentatively titled Cancer, from Despair to Discovery to Triumph. And it'll actually take visitors on a journey, not just throwing facts at them, but by drawing them into the story. So just as, as an example, when a visitor enters the exhibit, they're gonna be met by people, people of all ages and ethnicities and backgrounds, talking about what their lives are like as a truck driver, as a third grader, as a business person. And then, their lives were changed by one word, cancer. That brings people into the story, putting a human face on this, not just throwing facts at people. And then going into the exhibit, what is cancer? And the, the 12 essential characteristics that Hanahan and Weinberg described, which will allow people to explore and delve into that deeply. And in fact, understand why cancer detection is better because the cancers haven't developed all those characteristics yet, so they're caught early stages when they're treatable and curable. what? What we do to help the body fight cancer beyond just chemotherapy and radiation and surgery, but things like immunotherapy, cellular therapies, protein degradation, and again, imagine being able not just to read about what a CAR T cell does, but to actually climb in one. See how it's created. See how it's trained to recognize the cancer and travel along through the bloodstream. To see it find and kill that cancer cell. Those are the kinds of immersive experiences that that aren't available elsewhere and that we need to tell in order to engage people. Another thing is that we're not going to be trying to convince people of anything. What we're gonna try and do is open up what's currently a black box to the public to say, this is how science is, is performed. This is how discoveries are made, and this is how it's translated. We're gonna be very open about the fact that we're not always right. We make mistakes. There's a role of serendipity. There's the ethical aspect as well where we have, we have made mistakes over time. What were those mistakes? How were they detected and what steps were taken to correct them and prevent them from happening in the future? So, these are the things we plan for the museum, and I'm just, I can't wait. We're able to bring that forward and show people what we can do and tell these stories.
John Marshall, MD: I know you didn't ask, but I just can't resist. I think the CAR T thing needs to be bumper cars. You actually get in one and you bump into other cells, if you will, and you, you.
Mace Rothenberg, MD: right.
John Marshall, MD: There you go. I, you, you can just have that one for free. You, you,
Mace Rothenberg, MD: That would be great.
John Marshall, MD: We need to help you do this, and we'll certainly help promote the activity. We know it's both a fundraising effort, but also an awareness effort, that's out there to make this be a reality. And I,
Mace Rothenberg, MD: Yeah.
John Marshall, MD: know that all of our listeners hear the need and hear how your strategy and your project and all your past successes are funneling into a new one that'll be left for generations to come.
So, Dr. Mace Rothenberg, I cannot thank you enough for taking the time today to join us, and we really, really appreciate your time and we only wish you success in your third career as a museum developer. Mace. Thank you.
Mace Rothenberg, MD: Thank Really appreciate.
John Marshall, MD:
I cannot thank Dr. Mace Rothenberg enough. First at NCI, San Antonio, Vanderbilt, and Pfizer now in the next phase of his career is going to build out a museum that's gonna change the lives of all of us in our understanding of science and help keep truth alive. So, Mace, again, thank you very much for joining us.