In this special edition of DoctoRx Unscripted, Dr. Tania Small sits down with three of the most visionary leaders in oncology, Dr. Lillian Siu, Dr. Fabrice André and Dr. Howard “Skip” Burris, for a provocative conversation on data that has the potential to redefine the future of cancer care. They unpack cutting-edge findings from ASCO® 2025—from next-generation diagnostics and novel modalities to AI-powered trials, precision medicine, prevention and what’s coming next in oncology innovation. Dr. Siu, Dr. André and Dr. Burris are paid consultants for BMS.
ASCO® 2025: Cancer. Detected. Disrupted. Defied.
An exclusive edition of DoctoRx Unscripted with Dr. Tania Small®
In this special edition of DoctoRx Unscripted, Dr. Tania Small sits down with three of the most visionary leaders in oncology, Dr. Lillian Siu, Dr. Fabrice André and Dr. Howard “Skip” Burris, for a provocative conversation on data that has the potential to redefine the future of cancer care.
They unpack cutting-edge findings from ASCO® 2025—from next-generation diagnostics and novel modalities to AI-powered trials, precision medicine, prevention and what’s coming next in oncology innovation.
But the conversation goes beyond the data and tackles the decisions, behaviors and systems needed to shape real-world outcomes.
They explore how lifestyle modifications may enhance treatment efficacy and survival, and what it will take to improve global access to optimal cancer care through patient-driven science, purposeful action and lasting impact at the core.
This unforgettable episode spotlights the potential breakthroughs poised to detect cancer earlier and challenge conventional paradigms, with the goal of delivering better outcomes for patients worldwide.
If you're a clinician, researcher or advocate at the forefront of oncology, this is your front-row seat to the future told by the pioneers shaping it.
Dr. Siu, Dr. André and Dr. Burris are paid consultants for BMS.
Dr. Small (00:09):
Every day nearly 50,000 people around the worldhearthree words that change everything. You have cancer. One in two men. One in three women. Behind every number A life interrupted a story rewritten. This season we turn our focus to the fight of a lifetime cancer.
At ASCO 2025, I sat down with three of the most powerful voices in oncology. They have authored now over a thousand publications and are presidents of oncology's most outstanding professional organization. I'm truly honored to introduce you to Dr. Lillian Sue, the senior medical oncologist at Princess Margaret Cancer Center in Toronto. Dr. Howard Skip Burris, president of Sarah Canon Research Institute in Nashville and former ASCO president and Dr. Fabrice André, director of research at Gustav Rui Cancer campus in France. This is where science becomes action, where innovation meets impact. This is the future of cancer care. This isDoctors unscripted. Now let's get started.
Dr. Small (01:45):
Thank you everyone and thank you for coming. I'm going to ask you a question that's probably the hardest question for the day and it's about when you were in med school and you had those colleagues that you knew exactly what they were going to go into. What did your friends or colleagues believe you were going to go into and why did you choose oncology? And as you're telling us this, I would like you to introduce yourself. What do you do, your institution and then why? I'll start with you for Fabrice.
Dr. André (02:12):
My first thanks a lot for inviting me. So my name is Fabric André, I am a medical oncologist working in Paris, France. And so when I was in medical school, I was medical school in Grenoble. That is a city in the French Alps. I was doing ski racing. I really wanted to do sport medicine. I was fascinated by sport physiology. But then when you grow up in medical school, step by step you see the patient, you want to improve their situation. And also I became fascinated by molecular biology At that time it was growing. So then I switched to medical oncology.
Dr. Tania Small (02:50):
Got it. I thought now you did mention something about hematology as well.
Dr. Fabrice André (02:55):
Indeed. I love theology. I wanted to do hematology. I was doing some ski in New Zealand, so I asked a friend to take my fellowship and he ticked the medical oncology. It's okay. I owe him a lot of things.
Dr. Small (03:13):
No, thank you for that. What about you Lillian?
Dr. (03:16):
First of all, thank you for having us here. It's going to be fun talking to friends. I'm Lillian Siu. I'm a medical oncologist at Princess Margaret Cancer Center in Toronto, Canada. I wanted to be an oncologist from the get-go, so I basically took all the rotations that everybody has in oncology and did it and trade off their other rotations with me. So it was pretty much a interest from the get go.
Dr. Small (03:40):
Yeah. And what about you Skip?
Dr. Burris (03:41):
So Skip Burris. I'm an oncologist at the Sarah Cannon Research Institute in Nashville, Tennessee. I came out of college at West Point with loving engineering, math and economics and went off to medical school and it was an exciting time for cardiac surgery. They were doing the initial bypass surgeries and transplantation and I traded some rotations to do more cardiac surgery. It was really exciting for a while. And then the lack of patient touch continuity bothered me and I was a little nervous about what I was going to end up picking. And as I went through the various rotations, I found that I love the oncology patients. I liked working with the oncologist, liked the oncology nurses. And I really picked oncology as a career because they say you want to go work with people that you love to work with. And that was a big part of the decision and sort of learn the science after the fact.
Dr. André (04:41):
And you Tania, did you know which medical specialty you wanted to do when you were at medical school?
Dr. Small (04:46):
You know what, I thought I was going to go into OB-GYN. I loved it. I was watching these babies being delivered and I wanted in. And I remember even during the third year of med school, I was like, I'm going to do all the deliveries. And then I realized that that's not the piece that I enjoyed. It was actually looking at life and the potential of life. So I quickly moved from enjoying deliveries to actually the humanity and the human being that I wanted to treat. And that's what moved me in to medicine and then oncology.
Dr. Small (05:24):
So this year ASCO was filled with transformative data across the board. Out of all the sessions you attended, which data do you think is going to have the most impact over the next 12 months? And I'll start with you, skip.
Dr. Burris (05:37)
You're right. I mean there was data everywhere, exciting news everywhere, but this year, and it's not always the case, but this year the actual plenary session had presentations that are going to require our colleagues to go home and make a decision about how they're going to incorporate that information. The room was packed. I was joking. Even the bathroom lines were long like we were at some major sporting event. And yet as you went through the presentations, large trials randomized with answers that said, am I going to incorporate immunotherapy into the adjuvant, new adjuvant setting? Am I going to consider switch therapies in breast cancer? Am I going to do the biomarker and molecular profiling that we really should be doing for more patients at the time of their initial surgery to impact what my tribute decision will be? So I felt like all the presentations on that session, the oncologists around the world need to think about those results and there's not a right or wrong answer, but make a decision about how they're going to use that information to treat their patients.
Dr. Small (06:43):
And so in that case, what do you think for you, because you're still in practice, what do you think you're going to take home and I guess incorporate?
Dr. Burris (06:52):
So I have been beating the drum about not saving testing, not saving therapies where I've always believed better treatments, better testing, better therapies would come along. And so I'll go home and use this to continue to reiterate, what I believe is you ought to do the best testing and broadest testing on your patient as early as possible and you ought to consider utilizing those new therapies where there's data early on, not be a saver of a treatment.
Dr. Small (07:24):
I completely agree. What about you Lilian?
Dr. Siu (07:25):
I'm a head and neck medical oncologist. So there have been for the first time, two positive studies in head and neck cancer.One is keynote 6 89 that was presented in a CR and one is Nivo post-op that was just presented at ASCO. One is perioperative immunotherapy, one is essentially adjuvant immunotherapy. So I think when I go home we are going to actually literally have a meeting with multidisciplinary specialists, ENT surgeons, radiation oncologists, medical oncologists. We already planned that meeting on Friday coming up to discuss what are we going to do. I'm not sure we know the answer and it will be a very interesting discussion. I think the other abstract that I was very interested is the Canadian abstract, if I mayshowcaseCanadian work is Chris Booth's study about exercise in patients with stage three and high risk stage two colorectal cancer, that it was able to reduce death by 30% in follow-up for these patients in addition to all the standard treatment that they have had. And it's a cancer specific survival that they actually did not die from their cancer as a result of an exercise program. So I guess the question is can we extrapolate this to all cancers if that works for one cancer? So I think those two things are going to possibly change my practice.
Dr. Burris (08:50):
What you do in Canada, can it be incorporated into rest of the world, particularly the us? Will we be able to get folks to follow this advice?
Dr. Siu (08:59):
Well I think exercise is, I was going to say as easy as not easy, it's hard to make somebody exercise because you can do it for two weeks, you're going to do it for two years or 20 years and that kind. And that's why there was a coach involved in the study to actually have somebody supervise and encourage you. I'm not sure without one. It's that easy to implement. So we'll see.You need to coach every person in America.
Dr. Burris (09:24):
Great idea.
Dr. Small (09:25):
But then also then how do you pay for that I guess is the other question. So we have now these different dietary changes as well as lifestyle changes, but then how do you incorporate that, ensure our insurance company's going to pay for it? How do we, that's a good question,
Dr. André (09:36):
But I think Tania, there are ways to develop medical device on this topic.With digital medicine, wearable, maybe in the future the oncologist will check the acquisition of the data from a wearable of the patient with a kind of digital coach saying how much exercise the patient will do and has done. I think there are two questions that are really important in this is first, what type of physical exercise improve the outcome? I mean it's not all the same. Is it an Nairobi? Is it? And the second one is what is the mechanism? Because so if we understand the mechanism, well maybe we can also develop some drugs that will improve the outcome even better. So in fact, it's eye opener but it's also door opener. We are opening a totally new field. Maybe it's going to be about cancer metabolism, I don't know, but it's very important study I have to say. My first one was a head and neck presentation. The second one was the one on physical exercise. So in 30 seconds I had to find what was the third one? So I think I will select the one on trastuzumab Deruxtecanin patient with metastatic breast cancer with the overall express HER2 is the first line setting. The median PFS is around 40 months. And then I was discussing yesterday with colleagues said, well let's go back in the past 2001 with the New England Journal of Medicine, first randomized trial chemo versus chemo plus trastuzumab. The PFS was four months for chemotherapy. So it means that in around 20 years we move from four months progression-free survival disease control to 40 months. So it just tell us that with the knowledge of biology, the development of biotechnology where we can really have meaningful improvement for patient who are dealing with metastatic cancer. So when I was fellow metastatic cancer was meaning death in a few months. Now the first line disease control is around 40 months in some subset of breast cancer. I think the number impressedme a lot this 40 months.
Dr. Small (11:58):
I completely agree. And even in terms of I'm going to switch now to diagnostics and I'm curious to get your thoughts and I'll start with you for breeze on all the data in terms of liquid biopsy and obviously we've been talking about it for years and years and years, but even leveraging CtDNA to determine prognosis as we saw with IFI data or in terms of switching as we saw with Serena6. So out of curiosity, what are your thoughts please
Dr. André (12:25):
Circulating two more DNA meaning these are fragment of the DNA coming from the cancer cell that are released in the blood. So by a blood test we can detect this fragment of DNA coming from the cancer cell. Why it's important first because from the analysis of circulating tumor DNA, you can detect the mutation that can inform you on which treatment the patient should receive. Maybe we can agree that this is almost standard of care. I mean even in France we do it routinely for patient. The second application is early detection of cancer or early detection of relapse.And this is where I think we are going to have a discussion. Is it yes or not ready to be used? The third application is the opposite is when the patient has a cancer, whether there is a clearance of the ctDNA and if there is a clearance it means the outcome is good and maybe we can decrease the burden of therapy. There was a fantastic study in colon cancer where they could show that after surgery and local therapy and adjuvant therapy and before a joint therapy, there is no ctDNA it's possible to deescalate and to reduce the amount of treatment. So that are the three use case. I think it's level one evidence for detecting mutation. There are some very convincing randomized trial in colon cancer to deescalate treatments meaning no adjuvant chemotherapy. There is no CtDNA. And the question today is if we detect CtDNA rising CtDNA before the relapse of the cancer is detected by imaging, is it useful or not? I think that the reason that we're presented are promising. I think maybe it's a little bit early to conclude from my opinion that the detection of ctDNA before relapse on imaging really improve the outcome of patient. The drug that was tested in this trial called Serena six, that can be the strong Estrogen receptor degrader is effective. It's not the discussion. The discussion here is its CT detection before relapse on imaging useful for the patient. I can see SKIP is ready to make sure you get a chance
Dr. Burris (14:58):
You took the eight hours and condensed it down and I was leaning in because the idea of saying so much with fewer words is impressive and I think you outlined it into very nice segments. So no reason to repeat that. I think the challenges that I see in my world at Sarah Cannon communicating and working with community oncologist is justifying how often to do it that gets into the price, but we need to get it to a place where we can do it frequently. I think the other part which is a little bit of a hurdle is handling the information and then being forced to make that decision oncologists want and a get this result, do this therapy sort of thing. Getting some rhythm and guidelines on how often to do it is where we need to go next. But great overview summary.
Dr. Siu (15:52):
I want to interject too, I think have three points. One is I think the assay matters. Not every assay is made the same and not everybody understands it out there that if your assay is not sensitive, even if it's negative, it does not mean you have no residual cancer. So I think the assay is very important. And looking at the dynamic study in the colorectal cancer, the de-escalation seems to be a possible way forward, but de-escalation is much more difficult because obviously in that study dynamic three they escalated by adding a more intense chemotherapy. But probably it didn't help because there's cross resistance and the drugs matter. What you're going to do when you have the positive CtDNA result really is important. So I think if we think that one size fits all, just because you detect MRD, you add more drugs, it will work. I think that's a fallacy. It's not going to work. So I think these are the nuances that we have to think about when we think about ctDNA molecular residual disease switch therapy. Ithink there's still a lot to be learned.
Dr. André (17:07):
A lot of people think that the future transformation of oncology is going to come from early detection of cancer by blood tests. If this happens, I mean the life of patients is going to be dramatically transformed. Maybe we'll be able to early detect pancreatic cancer, liver cancer, highly little cancer. So probably the next two years we will have results of very important studies on this field that can potentially transform oncology and the life of millions of patients per year. So we are really looking forward for this.
Dr. Burris (17:43):
I just want to add one thought to that and I'm aligned. We've done a lot of work at Sarah Canon with those various clinical trials and they've been attractive and people are interested and Fabrice said a key thing about the highly lethal cancers. I think we've got to focus there. If you can pick up a pancreatic cancer early people get focused on breast and prostate that are slower growing and we've got more treatment options. And does early detection really make a difference, which I still think it does, but the early endpoint on highly lethal cancer should be where we really judge those tests.
Dr. Small (18:15):
But then, okay, so let's talk about that. So if you think through to your point pancreatic cancer, who do you know to create, how do you implement something like that?
Dr. Burris (18:22):
You describe a great challenge and in participating in the trials, we've had some great anecdotes of picking up a few patients and went to early surgery. But the fact is upper socioeconomic folks are who's using the test commercially right now. So we don't have the answer to your very good question.
Dr. Small (18:43):
I think that was one of the things I want to explore as well. We look at our different environments and we talk about liquid biopsy and if that's the future, how do get it implemented for you and more the rural community for you across the lower and middle income countries and which is a big focus of yours, how do we get that implemented within our communities?
Dr. André (19:00):
Well I think in Europe, Tania in Europe, the biggest problem here is the lack of market for diagnostic tests. If there is no market, there is no private investment. So there is no new device. So I think the next step for Europe in this topic of pretrial medicine is recreating a market for diagnostic companies.
Dr. Burris (19:21):
The only thought I'll add to it, and you alluded to it earlier, Tania, is this is a place to bring the payers to the table because treating earlier should be certainly much more cost effective. Exactly. So having them participate in this will be key.
Dr. Small (19:45):
I mean we can pull out all the economic models to show, right, if you can do much more preventative care or start or diagnose early, treat early, you're saving a lot of money in the backend. And one of the things I was thinking about is are these early studies, if you think through phase ones, there's been a lot of discussion about, obviously we've been doing a lot of adaptive designs, but how do we move fast? and shave off a lot more time, especially during this time, but yet hold true to the scientific rigor. So curious to get your thoughts.
Dr. Siu (20:13):
Yeah, I think obviously there's a competitive market where when you do your trial you want to not share that data until you're finished. And I think when your study is finished in early phase, I think that data should be shareable because it's sort of the hopefully post competitive phase that you are able to actually learn from each other and how many drug X targeting target Y out there. Many. And we know that for example, companies all have very similar pipelines and yet by the time we hear of five of them or six of them fail, you still have four or five of them going on and that data is not shared, that data is not learned. And I think it is a pity that we're not able to do a lot of iterative learning on negative data. I understand positive data is hard to share. I think negative data can be shared that will eliminate us not wasting our time, our resources and obviously our patient's time to go into studies that probably has a very, very little chance of succeeding. And I think one of the area I'm very interested is how we can actually leverage preclinical published sound lines models, AI, whatever it be on clinical trials and real life evidence and post clinical trials, real life evidence and keep learning as a model. Maybe we can do more federated learning. You don't send it out but you can train your model locally and then feed it to the world. I think that's the only way we can actually learn quickly together.
Dr. André (21:55):
I think the way you can also accelerate things is through cancer classification.Our cancer classification have been done for local treatments. Now we are in the era of molecular oncology, meaning any drug is targeting a specific protein specific molecule. Specific process for me does not make any sense. We say look, we start with melanoma two years after we do kidney cancer two years after we do lung cancer because the molecular determinants of drug sensitivity are the same in lot of cancer. So we should really move in addition to organ based classification to have molecular based classification going pan cancer or multi cancer. I think that could dramatically accelerate drug development. If we look at anti PD 1 for example, it took more than 10 years before some group of patients defined by a disease defined by an organ got access to anti PD-1. But again, the molecular determinants of sensitivity of anti-PD-1 one were exactly the same as the melanoma or kidney and cell lung cancer. So I think that could dramatically accelerate drug access.
Dr. Small (23:12):
How do we change that? Because most of us are focused on a particular tumor type even in terms of practice. So how do you make that paradigm shift?
Dr. André (23:21):
I think this is the work of scientific societies, ASCO. I mean these are very strong stakeholders. So if tomorrow this organization are saying, look, in addition to the conventional way of classifying cancer, we can agree on another way to classify cancer based on molecular alteration. And of course ACR can be a major player on this question as well. That can really change the defeat dramatically and accelerate and of course regulatory agency have to be involved in this switch of classification. But in our analysis we think it's a major challenge for drug development.
Dr. Siu (24:03):
A lot of the problem is that it's not funded in many jurisdictions. NGS is just not available on every patient. So it's challenging. I completely agree with Fabrice that we need to learn not just on histology, we need to learn about the biology and yet NGS is not available so you only have half of the equation and it's hard to contribute data when you don't have the second half. And I think that's something that perhaps the funders and the payers need to think about how to actually make it more available perhaps especially in cancers where there are actionable targets. Right?
Dr. Burris (24:36):
Going back to what we were all saying, if you're going to fail, fail fast and that helps everybody stays resources. Patients don't go on effective therapies. The other thing I comment on going to the NGS piece, if I'm a pharma biotech with my drug, I want to know everything I can about that patient so that I can then, and this is where AI and other analysis can come in, why didn't it work in those groups? So people say, well give me an example. I mean go back to many years ago if we treated trastuzumab with for everybody, it wouldn't have gotten approved if we hadn't found the subset. Cetuximab struggled till we realized that there's a whole group of colon patients with K-ras that weren't going to respond. So there's simple examples like that and now that we're with better agents, better targets, better understanding, it should even be more relevant. We should have dozens of those examples and we probably do.
Dr. Small (25:34):
And that's why I was going to ask next becauseobviously there's been a lot of companies talking about AI and leveraging AI to do better predictive modeling, to understand resistance much better. Who are your responders who won't respond? How can we start using AI to develop better studies, to develop better drugs?
Dr. Siu (25:52):
I mean AI is such a buzzword. Everything is like AI is like everything tastes better with bacon on it, everything that looks better when you have AI in your design and your model. And I think we're still at the learning stage of how to leverage AI and yet the learning curve has to be really steep. To be honest. I think it's a good time because we have technology and biology really both side by side each other and they're racing to be who is which one is more relevant and they both are. And I think we have so much data that we can feed into these models and the important thing is to really understand when the output is correct or not. And I worry about hallucinations. I think the future is very exciting with these digital pathology AI models, generative AI models, but we just need to be a bit cautious in the output.
Dr. Burris (26:44):
So on the AI front though diving in, but I have our molecular team continually provide me slides that are called the perfect patient. So I'll give you two quick examples that I just gave at a recent lecture. The perfect pancreatic cancer patient for a trial, they had a very specific KAS mutation that this biotech company desperately wanted. At the same time they were mtap deficient. So they were the perfect patient for the PRMT five. And so with trial to put 'em on and both those companies are going to judge in a silo or a vacuum. So then fabrice, I had a patient classic estrogen positive breast cancer patient. Then our molecular team pulled out from one of the sites who had a TMB over a hundred. So we don't give immunotherapy to an estrogen receptor positive breast cancer patient. But with a TMB greater than a hundred, she was the perfect patient for several IO trials. So what is it about the, you're going to need AI to understand a
Dr. Siu (27:43):
Combination.
Dr. Burris (27:44):
AI has got to hopefully help me, help us figure out that all these patients we've proven with NGS that every patient really is unique.
Dr. Small (27:56):
So as we were talking about AI and one of the things that I'm really curious about is how do we leverage AI to even understand our responders versus non-responders and use that much more to predict. So how do we leverage AI to get smarter about that?
Dr. Siu (28:12):
So it has to be taught and the only way it can learn is we give it data from experience, real world negative trials, positive trials. And it keeps go on to an iterative cycle of teaching and learning. And I think this is why this kind of process of having data sharing is really important in my view
Dr. André (28:31):
Tania, this is going to become a major role for academic institution. That is the issue with AI that they need large number of high quality dataand this can only be delivered by institution who are committed to provide data or very high quality. So this work of generating data is going to be more and more important. Then I think about AI of course is going to probably to transform oncology still we need to be realistic. We still need brain to invent, discover what is a new dimension of biology that is important, being able to design the experiment on the way that the AI will not be able to do it. So I think I'm very optimistic about AI is only thing that we need to rethink the role of academic institution in this new era. Plus we all have to realize the most important predictor dimension of biology is the one that has not been discovered yet. And this is still in the hands of the human.
Dr. Burris (29:41):
And I'll just add the one hope I would have for AI is if we think about novel endpoints, we're at a place now with some diseases, there'll be continued fights of do you have to show overall survival? But with certain mutated cancers where people are going to do well for years or even thinking about tumor classifications like CLL or some of the bone only prostate breast, it's just not realistic for us to wait on advance for survival. We've got to have other endpoints there. And the other point I would bring up is the parts of the human condition that are affecting these therapies. The fact that patients that are overweight seem to do better with some of the immunotherapies, there's other biologic characteristics that we need to accumulate all that data and hopefully AI can sort out what some of those issues are as to why people do better or not.
Dr. Small (30:46):
Since you went into overweight healthy living, I want to actually talk about that because like I said, that was a big focus for ASCO and we know that weight gain smoking, we know sanitary lifestyle all contribute to your increased risk of cancer. What do we know about lifestyle and its association with cancer and what should we be doing as healthcare providers?
Dr. Siu (31:09):
Well I think that the obvious ones are the ones we already know. Smoking is bad for you and drinking a lot is not good for you. I mean for the cancers that we already know. But I think for the new areas, exercise seems intuitive but the mechanism like Fabrice said is not clear. It is not because they become healthier just because they stopped drinking and doing good thingsbecause their cardiac risk has not changed, for example. Or it's similar between the two groups. So I think we have a lot to learn. For example, my psychiatrist in my hospitals are interested in people in distress. Their psychological condition affect their response to immunotherapy, what's happening to your cytokines and all your enzymatic metabolic systems. These are complete unknowns to us and we spend so much time on tissues, blood and everything else. We forget about some of these other areas that are probably much more challenging to be honest, to measure. And I think they do factor in terms of treatment and responses and resistance.
Dr. André (32:16):
Absolutely. I think Tania, I think maybe two point on this topic. First a major component is social determinants of outcome. We have a French epidemiology study has been fascinated because each time we address a question, we always see social determinant of outcome coming first to predict toxicity, quality of life, deterioration of quality of life, et cetera, et cetera. So this is a very serious issue that for oncologists we don't have this in the radar, so we need to create awareness on this question of social determinants of outcome. The second thing I wanted to mention is all the work from Qlik Institute about the role of macrophages on cancer promotion. This can be transformative on the way we even perceive the cancer because maybe we can modulate this by blocking IL one or different other mechanism. So this is very important but also maybe we can predict, but more importantly is going to totally change the way we, again we classify disease.Tomorrow we'll see everyone or you have high level of chronic inflammation, you are predicted to develop cancer, cardiac disease, neurogenerative disease, et cetera, et cetera. So probably the trunk of the disease is going to be shared between many disease. So these things of mild with cell macrophages as a determinant of and predictor of further disease is going to be something very important for the next decade.
Dr. Small (34:05):
And you're right because I think every therapeutic area is exploring that. And as you guys know, I did a show before on Alzheimer's, you're going to hear us talk a lot about that and inflammation is prediction and its prognosis when it comes to Alzheimer's.
Dr. Siu (34:17):
I want to ask you with obesity, do you think GLP one agonist is going to have a big role in cancer reduction, cancer mortality change?
Dr. Burris (34:25):
So with the dramatic uptake of those drugs, we should be able to have an answer in the very near term. And you would think that that's a place where AI could help if we can aggregate the data quickly as to have that level. And then the next step of that, I was going to comment on a minute ago, is part of that success going to be reducing the markers of inflammation and is it going to be reductions in stress and being able to measure that? Because a common question I keep getting asked by colleagues and friends outside the profession is younger individuals getting cancer. And I think we used to consider that anecdotal, but now it seems to be clearly a prevalent issue. And so environment diets are part of that, but much of the tools we have now allow us to lead pretty sedentary lives. And then it also feels like stress is higher than it's ever been. And so measuring how those are part of the impact has got to be part of the story.
Dr. Small (35:22):
And even as we continue to talk about health, there's a big discussion about microbiomes and I know there's some recent data was shown that even with when it comes to resistance of for example, PD ones and once you change the microbiome, once you change the environment, you get better sensitivity. What are your thoughts on this?
Dr. Burris (35:44):
So a shout out to my wife and I gift though a young investigator award every year and we've had one of Lillian's outstanding researchers be a recipient and this year our award winner is a researcher out of California who's studying exactly that, and we don't pick the project the review committee does, but she's studying the fecal microbiome. The tissue microenvironment from patients who relapsed on the neoadjuvant checkpoint inhibitor trials that did pretty well. But what was it about that group that didn't get the success? And she's got some information suggesting that the microbiome there might really be a factor to a key point we've got to study.
Dr. André (36:31):
But I think Tania, I agree it's interesting. What we are missing still is a large randomized trials. If I do fecal transplantation, I change the outcome of the patient and the day we have it suddenly it's going to attract a lot of attention, lot of investment, new clinical trials and then it's going to grow dramatically. Today it's a little bit looping a little bit. So we have a lot of retrospective studies. There is something happening, but it's difficult to de exactly which bacteria is important, which network of bacteria. So I think we still miss this bigger data showing clinical utility and then things will go very fast and very broad.
Dr. Small (37:14):
And maybe someone just for our listeners, if someone wants to explain what the fecal transplant is
Dr. Siu (37:20):
There are different ways to do it. You can take stool from patients who are very good respondents from one immunotherapy drug and give it through colonoscopy to another patient who is going to receive immunotherapy in the hope that you're going to directly transfer group organisms into their gut so that they can actually have a higher chance of responding to immunotherapy. As you said, there are oral formulations that can do the same either in the form of bacteria or encapsulated stools or different formats.
Dr. Small (37:51):
Thank you for that.No, that's a fascinating area. So we're going to talk about disruption. So when we think about disruptors in the field, we are looking at different modalities, whether it is ADCs, bispecific, tri specifics, protein, degraders, radioligand therapies, there's a lot happening in this field. What excites you the most and where do you think the field is going to go next?
Dr. Burris (38:16):
Lilian, I'll let you go first.
Dr. Siu (38:17):
Okay. It's hard to predict which one will, it's probably going to be combinations thereof. I'm excited about vaccines because I'm interested in the molecular residual disease space. So I think in that group it's hard to give somebody who has molecular residual disease, prolonged intense toxic therapy. So I think the attractiveness of having a personalized therapeutic vaccine is very exciting. And obviously we already have preliminary data from some diseases, pancreatic cancer, kidney cancer, that perhaps we are able to trigger enough of immune response to perhaps eradicate an intercept in those patients with high risk disease that we just talked about with detectable ctDNA. So I think I'm very excited in that and that data still needs to be matured through randomized trials. It's still a bit early, but certainly I'm very interested in following that path.
Dr. Small (39:12):
Yeah, no, completely agree. What about you Skip?
Dr. Burris (39:13):
I would echo the sentiment on the vaccines. I think we had some early starts that were too broad. It's going to get more specific and going to minimal residual disease, early adjuvant therapy, that's going to be the place to really study those. I'll throw in that I've been amazed by how quickly the bispecifics and now you're hearing about tri specificsBispecifics bi functionals and having had some experience with those and seeing those therapies overcome resistance to traditional therapies. I have great hope for that. I have great hope for it's that ultimate combination of science and engineering. One of our common mentors, Dan Von always said that he thought engineering would play a big part in curing cancers. And I think he's going to be proven correct again that the engineering is going to help us have the better molecules there.
Dr. André (40:07):
I fully agree what has been said, I think biotechnology,are going to change cancer care, but we all have to keep in mind, and as Skipp was saying, we can improve drugs only if we understand the failure and the mechanism of action. So that put all the academic colleagues at the center of the research, we need to understand from patient sample what's wrong, what's right to go next step. Maybe that two point first, I've been quite impressed by radiotherapeutics. I think it's going to grow. We still don't know how it's going to be implemented, a lot of work, but it's here, it's going to grow. And then the second thing, because you talk about disruptive, it's something that we would like to do since five years, we don't know how to move it forward. There's no more and more we are going to a situation where we can really model the biology of cancer in each patient. The logical next step will be to create a drug per patient.SoIf you understand the mechanism, you understand the protein. We have AI to design drug. We are not so far to create one pill, one antibody, one complex drug for patient and the only issue is the time and the price it would cause. But I think as a concept we should start working on this.
Dr. Burris (41:24):
Do you think on the radioligand front there's enough targets that are going to be suitable, meaning tumor specific not found on normal tissue?
Dr. André (41:38):
Oh, I think so. First, there are a lot of work on this topic, so I don't think we have a clear answer to date. I think biggest institution in the world are working on what they call surface. So discovering new protein that are specific to cancer and maybe we'll have some surprise, maybe some proteins from a retrovirus over expressed in cancer. Then the question you're asking is very interesting question from a pharmacology perspective, what do we call a normal tissue? And finally, do we need to compare the protein of the cancer to any normal tissue or should we just spare the most important tissue like heart, kidney, brain? And I think this question for me is also, but it's a crucial question. If we want to discover new cancer specific target, I don't think we should compare to any normal tissue. I think we should limit to the tissue where if you target this organ is going to create major toxicity
Dr. Siu (42:38):
I mean that's going to be relevant for ADCs, it's going to be relevant for CAR-T’s. I mean I presume knowing what is expressed on the surface, what internalizes, which one's functional, which one's not functional and all the normal versus non-normal distribution.
Dr. Burris (42:55):
I guess I didn't clarify my question. That was a great answer and I agree with it and I feel better hearing you say that. And when I think about an A DC, you think about off target chemotherapy effect that will go away as opposed to we always think of with radiation that once we've done it, it's done. So is there going to be a different level of concern? But I certainly share your sentiments and I think you get to a key point about there's organs we must protect.
Dr. Siu (42:22):
Well that's why the payload in these drugs are going to be very important, whether they're going to have very short distance and not damage your deep organs andThe half life, right? Yes.
Dr. Small (42:36):
Throughout this discussion, we've beentalking a lot about sharing data, understanding both from an academic standpoint, from a society standpoint, from even a pharma standpoint. How do we work together? We understand obviously the environment has changed and let's be clear there's less funding for research as well. How do we work together so that we don't drop the ball and we continue to move research forward?
Dr. Siu (43:59):
Yeah, I mean if you think about it, patients want to share their data a hundred percent.Physicians want to share their data for sure, because we all want to learn to see what is going on and we don't want the field to move very quickly. We wouldn't want it to stall. So what are the barriers? I think a large part of it is legal. And I think we need to work on how do we overcome the legal concerns and legal barriers. Of course we want to provide privacy. That's completely understandable. But at the same time, there are many ways we can do this kind of sharing without breaking these privacy concerns or similar concerns. And I think this is where we really need to work that framework that everybody feels comfortable and yet we can move the field much more faster than we are now.
Dr. Burris (44:46):
Agree that we've got to empower the patient. There needs to be some standardization of when you're moving into the situation for the first time with your physician, that you agree to share your data with the appropriate provisions to protect privacy. I mean the data is the patients, there's intellectual property on drug development and those factors be brought in, but it's the patient's data. They're going to benefit from sharing with each other and we've got to continue to push that initiative.
Dr. André (45:19):
I think Tania, I fully agree of course regulation especially in Europe is a major buyer to share the data. But I wanted to add something else. We should also add in the evaluation of academics, whether they have contributed to large database, how many download, et cetera, et cetera. Myself, I had my team evaluated, well a few time ago. We have added in our evaluation how many times our data were download by external teams. And the evaluation committee was very happy with this. So I think it's also about leadership of organization, institutions and society to reward people whoshare really the data.
Dr. Small (46:09)
Now I'm going to shift tosomething that I think is near and dear to all of our hearts, and that is looking at access and looking at access for patients. Because obviously no matter what kind of innovation we bring forward, no matter what kind of breakthroughs we bring forward, if it's not reaching patients, then eventually it's for Naugh. How do we work to improve access? And I'll start with you, skip, since I know that again, you work in a lot of rural communities. How do we ensure that our medicines are reaching the patients? Our studies are reaching the patients.
Dr. Burris (46:39):
It's a critical issue, democratization of care, access to care, and it goes beyond even race and socioeconomics. I mean sometimes it's geography, sometimes it's social support system that the patient has. All those factors play together. So we've got to recognize that. And certainly with all the modern delivery techniques and technology, there should be no barriers anymore with regard to geography. And we can't expect individuals to travel to the great institutions, but they can't get to those cities. I think the other part goes back to the data issue, understanding and having those patients aggregated in so that we can look at populations of patients that might benefit. And that's another part of the futility success analysis. And then I'll shout out for asco. I think one thing that ASCO's taking very seriously is this idea of getting rid of the copays and the patient participation in paying for their cancer care. Yeah,
Dr. Small (47:40):
Couldn't agree more.
Dr. André (47:43):
I think Tania, from my perspective, first, the first step was to be aware of this problem.When we are aware of the prem, well it means that we can start working on that. So I think the first step has been done. I see two direction on this topic. First is short duration therapy. Part of the pre is that the fact that treatment have become too complex, too long. So I think when a patient is presenting a cancer that is highly sensitive to a drug, we need to be sure we reduce the duration of therapy because by reducing automatically, we reduce dramatically the cost of the treatment and we make it more accessible. So this is a major effort that we must do in the field of academics about deescalation therapy. The second one, and Skip mentioned that is about technology. We are discussing about AI. Probably AI is going to revolutionize access to treatment in low medium income country because when we apply AI to images, or maybe we can detect microsatellite and stability, maybe we can detect no, all this feature that define very high sensitivity to treatment. So I think for me the two pillars, the two solutions are short duration therapy and moving easily accessible technology to where some country where there is some issue of access.
Dr. Small (49:11):
How close do you think we are to being able to implement that or how receptive our treaters and researchers?
Dr. André (49:21):
From my experience in the few project we did, I mean we have a lot of engagement from everyone and I think everyone want to go in this direction and we have really good feedback from many stakeholder including startup companies working on the field of AI, including government, including pharmaceutical companies. So I think everyone want to do something. You know why? Because there is a major ethical issue behind. The major ethical issue is I give you the example of Immunotherapeutics to patient with MSI. It has become a major ethical issue that some patient in the world don't have access to this. This is a curative treatment for patient with highly little cancer. So we go beyond the general political question, it has become an ethical, ethical issue. So it's becoming very, very serious.
Dr. Small (50:13):
Yeah, no, I couldn't agree more with your thoughts, Lilian.
Dr. Siu (50:17):
Yeah, I guess I'll go more to the trial level. For every clinical trial, I think it'd be good for us to think about who are we recruiting? Do we need to have, for example, patient navigators and patient advocates and to really understand how to make the trial easier and more implementable. Of course, we want pharmacokinetics every day for the rest of their treatment cycles forever and ever. But are they needed? And do we need every visit to come down to the cancer center? Can some be actually being more local? And I think navigators can help with a lot of that. And obviously patient voices need to be heard and sometimes when we review protocols, we think it's easy, but it's not. And I think having that kind of patient engagement and patient advocacy for every protocol would be very helpful.
Dr. Small (51:09):
I mean to your point, sometimes when you look at a protocol, so much of it's just copied and pasted, right? Totally. And then you haven't asked yourself the question, how much of this do you really need? Or even having discussions with the regulators to say, do you really need all this PK data? Do you need all of this? Because now your patients are excluded of that.
Dr. Siu (51:29):
Yeah, absolutely.
Dr. Small (51:31):
So I'm going to do a quick round robin for final question. We have, again, this is really focused on HCPs, but we also have a lot of younger HCPs, whether they're fellows, residents, or just starting their career in oncology. May I start with you? Skip to go around any advice that you have for them, something that someone told you or something that you picked up throughout your years?
Dr. Burris (51:57):
Fabulous question I'm worth thinking about. To me, the idea of finding that person who you really trust and looking around and interviewing the elders in your group. And they don't have to be a lot older as to who you think is really going to be a mentor for you or a sponsor for you. They're subtly different, but I think it's worthwhile just not taking that person who might be in your tumor type or in your disease area. I've been very fortunate with those folks who've helped me, but that's got to be a two-way street. And I think it is worth really being diligent about thinking who do you want to be that advocate to work with you? Yes.
Dr. Siu (52:40):
I would say while we want our early career investigators to focus, it's also important for them to also think out of the box sometimes to learn something that you would not normally feel comfortable to sit in a lecture for or read a book on or read a paper on. Just sometimes it helps you stimulate that part of the brain that you haven't used because you haven't been thinking about that at all. And it could be applied back to where you want to focus. I think just more, what's the word? Disruptive, transformative, more out of the box.
Dr. Small (53:13):
There's something that I usually say to people and especially to students, if it has been done, then we can do it. But if it hasn't been done, then we must create it. And to me as oncologists, we have to continue to push the boundaries, be disruptive, ask the questions, and actually if there's no response, come up, find the answer and continue to pursue it. So can agree more. What about you?
Dr. André (53:34):
No, me. I think Tanya, I would really encourage young colleagues to go oncology because I think it's really a specialty that can transform you as a man or woman because you are really, I mean at the center, at the core of what is humanity, I mean you are dealing with patient, some of them are going to die. So you really learn what is the most simple but most important thing of human beings. So I think it's, for me, it's real, especially that has really transformed myself. So I really encourage colleagues to go in that direction. We know in this era where there is ai, complicated things, sophisticated, going back to the most simple and important thing that is human being, life, death, family, et cetera. I mean, we all need to go back to all these things now.
Dr. Small (54:23):
And with that, thank you so much. This has been fantastic. So I mean, again, just thank you all for being here. And obviously we have, to me, the giants in the field that have moved the needle, seeing where you have moved the needle for patients, for people, for humanity, is exceptional. So thank you so much for everything and thank you for being here. Thank you for speaking and teaching and sharing your knowledge with the HCPs that will listen. I appreciate all of you, so thank you.
Dr. Siu (54:49):
Thank you for having us.