Dr. Vail: And the other would be how can we, through this process, have what's now called comparative oncology, learn and inform human treatments and human diagnostics? And the two are really very intertwined now, whereas I almost can't separate them. If I get involved in a clinical trial whose charter is to help human health, to inform human clinical trials, I always make sure that there's a bidirectional component to that.
Dr. Venable: Welcome to the Veterinary Cancer Pioneers Podcast, the show where we delve into the groundbreaking work of veterinary professionals who are dedicated to advancing the field of veterinary oncology. I'm your host, Dr. Rachel Venable, and I'm thrilled to embark on this journey with you. This episode is produced and brought to you by ImpriMed, pioneers in an AI driven precision medicine for veterinary oncology. ImpriMed’s personalized prediction Profile helps you make confident treatment decisions for canine lymphoma and leukemia patients by predicting how your patient will respond to multiple chemotherapy protocol options. If you've never used it before, US-based veterinarians are eligible for 50% off their first Personalized Prediction Profile with discount code ‘PODCAST’. Learn more at imprimedicine.com. That is imprimedicine.com.
Dr. Venable: Hello and welcome to the Veterinary Cancer Pioneers podcast. Today we have the distinguished guest, Dr. David Vail. I'm so excited to go into his career. He is certainly one of the main pioneers in our profession. He has authored more than 170 scientific papers, over 50 book chapters. He's a co-editor of the widely used textbook of Small Animal Clinical Oncology. The one that I was told, if I can read it all, maybe I should go into oncology. So I certainly have multiple copies of that book. Really enjoy it. He's been the president of multiple prestigious societies and scientific advisory boards. He's currently a professor at the University of Madison, Wisconsin. And honestly, your bio, it could probably take us ten minutes to go through. So thank you, Dr. Vail, so much for being with us today.
Dr. Vail: Yeah, that just means I'm old, right.
Dr. Venable: I think it’s extremely humble. But we'll go with that. So at the beginning, I always like to ask people how they got started in veterinary medicine. And also what got you interested in veterinary oncology?
Dr. Vail: Sure. Well, veterinary medicine was you know, what pointed me towards that was pretty typical reading that, you know, the James Herriot novels as a kid and having pets in the household. There was always something that really interested me. And from a very young age I got involved in that. I remember taking our, you know, family pets to the veterinarian. And then I initially wanted to be an equine veterinarian. Part of that was quite selfish. I used to, we worked in a family business all through my youth. We had business on the Alaska Highway up in Canada. And in my spare time, what spare time we had, I did a lot of horseback riding, and I always remember the veterinarian coming out and in his van, and the veterinarian that serviced the stable that I was at, he would step out of his van. And he was this very tall, handsome, red-haired veterinarian that all the teenage girls at the riding facility would swoon over. And I figured, hey, that's got to be a good gig. So, I mean, it didn't work out that way for me, but that's where I wanted to start. As far as why I became an oncologist, you know, a few things. I wanted to be an equine vet to start with, and really, when I got into veterinary school, just really the science started to take more of a hold and there was more of an opportunity on some of the companion animal side of things that not that horses aren't companion animals. I also had a couple of experiences growing up where my best friend's mother passed when we were young, of metastatic melanoma. And one of the girls, teenage girls that I used to ride with passed from osteosarcoma. So there was certainly that in my history. And, that just kind of accumulation of events really led to that kind of, you know, an odd story. When I was in large animal medicine as a student and taking care of a horse with hematuria, I actually diagnosed that horse with transitional cell carcinoma. And I figured, hey, you know, this is going to work for me. So yeah, that's pretty much how I got into oncology. During my internship, I was lucky enough to match at Colorado State, which at the time was really a pioneer, and in starting a cancer practice within an academic center. And so I was really lucky to have Steve Withrow, really the father of veterinary surgical oncology, and Ed Gillette, the father of veterinary radiation oncology, as my mentors. And they really helped me get extremely interested in oncology. And so I went back and practiced for a couple of years, knowing that I would eventually do a residency and I chose medical oncology.
Dr. Venable: So how would you say practicing today is different from when you started back in the 80s during your residency?
Dr. Vail: Yeah, so we're talking 40 years of difference, right? So, you know, Greg McEwen, one of my mentors, started his cancer practice at the Animal Medical Center in New York City. And he worked; he had a co-appointment at Memorial Sloan Kettering, the very famous human cancer center in New York. And he used to describe back in the day, back in the late 60s, early 70s that the practice that veterinary oncology is you made the diagnosis in the morning and you did the postmortem in the afternoon and that's sunshine. What the state of the art was back then during my residency and internship. So we're talking going ahead another decade, late 80s, mid to late 80s. The technology certainly wasn't what we have today. There was certainly a smaller group of like-minded individuals nationally and internationally that were interested. The idea of the human-animal bond was really just entering kind of a golden period of the human-animal bond, and, you know, we talk and I use this in lectures sometimes that that the family dog, for example, back then was the Snoopy-like dog that from Peanuts, he lived outside, you know, he was fed dog food. And every once in a while, you know, they interacted versus the, you know, that's what we have today, where the companions are really living with us, eating with us often family members. So there's now, you know, a lot more client intervention, caregiver intervention on the internet, looking for what are the best treatments or the most novel treatments for advanced disease. Back then, we were really out in the wilderness, just kind of discovering things. Certainly we had a few decades of physicians based-oncology you to line up against. But, you know, dogs aren't well, people and cats aren't all dogs. And we had a lot to learn. We were more reliant, probably on our clinical skills back than our physical exam skills than today, just because of the lack of technology. And, you know, it was just every day something new and exciting as it still is. I mean, that's the good thing about practicing veterinary medicine. I learn something every day.
Dr. Venable: I think that's great. And I'm sure you have all kinds of stories with Withrow and some of those guys back then, and it all sounds really interesting. And I'm wondering, how did you guys navigate treatment back then when there wasn't a lot of information? I feel like with oncology, most people want numbers. They want stats, and I always like to try to practice evidence based medicine when I can. But there's still plenty of cancers and tumors that we don't have much information on. But just thinking about in the beginning, when you guys were getting the foundation for all this, how were you able to navigate what to tell owners or how to choose treatment?
Dr. Vail: Yeah, I mean, we were pretty much followers at that point. We were followers of physician-based oncology. For the most part. There weren't any textbooks yet. I mean, the first edition of Withrow, you know, was just being developed at Withrow, McEwen, which is now the textbook that we've continued on and we're in the seventh edition. But back then there really wasn't that there wasn't the ability to there weren't a lot of publications other than, as I said, necropsy publications and pathology publications. Everything was based on necropsy reports. And that's not very helpful from a clinical standpoint. Now, CSU, Colorado State at that time had that with Ed Gillette's group, had some major funding through the National Cancer Institute, and that really led to collaborative approaches with the physician based cancer centers that got us kind of into the stream of discovery. And that was really important. So we spent a lot of time doing rounds with the physicians and the scientists in the area. There was a core group, I mean, back then, the Veterinary Cancer Society, there were about 75 of us that used to meet every year at Purdue University. And now, of course, meets, you know, all over the country. And there's meetings now that are 600 to even 1000 people. And back in the day, there were 75 of us in a small room. And there's certainly advantages to that. I mean, we got to know everybody and we got to interact much more strongly with the movers and shakers at that time. So, again, to answer your question, we really relied on what was known in humans and tried to be all we could be was anthropomorphic and try and trance for that. But we had some amazingly interested individuals on the veterinary side that really wanted to look at it from a species standpoint and not just translate on the human side. So my other mentor, Greg McEwen, when I took my first faculty position at Wisconsin, he was really the first veterinarian that I knew of on the medical side of things. Ed Gillette was doing radiation and Withrow surgery, but Greg McEwen was the one that really felt that allowed us to consider the inclusion of companion species in clinical trials and as part of our practice.
Dr. Venable: Yes, you've done a lot of clinical trials over the years and lots of great research. What would you say has been the most impactful from your research?
Dr. Vail: Well, I tend to break my research down into really two categories. The one category is that the charter or the focus would be on companion animal health. So companion cancer specifically. And the other would be how can we through this process of what's now called comparative oncology, learn and inform human treatments and human diagnostics. And the two are really very intertwined now, whereas I almost can't separate them. If I get involved in a clinical trial whose charter is to help human health, to inform human clinical trials, I always make sure that there's a bidirectional component to that. That is that we will get that information back into my clinics. At the end of the day, I'm a veterinarian, and I want to help out companion species that develop cancer. And they're certainly classic examples of where we've done that as far as, you know, kind of individual examples that have helped companion animals, specifically the trials, in the early days that we were the the center that did trials on drugs, like Cerenia, the most common antiemetics used in in cancer practice and not just cancer practice. And that drug has made a profound difference on our companion population.
The initial work that we did with Tanovea, the very first cytotoxic chemotherapy FDA approved for use in dogs, and we modeled that we got together with a human biotech company and developed that, and eventually it went on. The license was picked up through veterinary sciences. And as I said, is the very first cytotoxic chemotherapy approved for use in dogs. So that was, you know, what I think of as an accomplishment where we helped out the flip side is that Tanovea was initially our work with Tanovea was to inform human clinical trials. And so that's a real classic example of the bi-directionality of the clinical research that we've done in the past. That is that we informed human trials, but that drug was licensed for use in dogs. And now that is that drug that we reach for in some circumstances. So that's important.
And then, you know, other things that I think have been accomplishments are drugs that have gone on that not necessarily have come back to us and veterinary oncology for a variety of reasons: availability, cost, etc.. But some of the immunotherapies that we're looking at now, and in particular combinations of immunotherapies and other therapies that are now have sprung human clinical trials. We have a trial here at the Human Cancer Center, the Carbone Comprehensive Cancer Center. That was driven by our clinical trial to look at combinations of therapies, immunotherapies in companion dogs with naturally occurring tumors. And again, all of our clinical trials are involved, tumors that occur naturally in our companions. Cancer is the number one cause of morbidity and mortality. And in the aged dog population. And so, we're not creating these cancers. These are natural events. And so it's gratifying that, you know, in the past, as I've said, we were followers of physician-based oncology. Now we can be leaders of that and informing them on the human side as well. So it's been a really great collaborative experience.
Dr. Venable: I love that, I love how we can help people but help animals. And in the beginning, I thought it was great how you said you were really following physicians and learning about what to do in veterinary oncology. But now, as things are becoming more advanced, actually some of the physicians are following what we're doing in veterinary oncology. So that's really exciting. And to go into more technologies and immunotherapies that you've been talking about, I know you've given some lectures on these recently, especially Gilvetmab, which is a checkpoint inhibitor that we now have in dogs. Can you talk a little bit more about Gilvetmab and just educating some of our listeners on how it works and how you guys are using it and what you've seen so far?
Dr. Vail: Yeah. Well, you know, that the hot area right now universally is immunotherapeutics. So, you know, that's one of the reasons that as you age, your cancer risk increases, both in our companion pet populations and in humans. Is that just like the rest of our bodies, our immune system gets tired. And it's designed to seek out abnormal cells before they develop cancer and kill them. But as we age, that system gets tired and exhausted and loses the ability to do that. And immunotherapeutic strategies are really designed to take an aging, tired immune system and turn it back into a young, vibrant immune system that will recognize these abnormalities and clear the cancers before they start would be ideal. But after they've started to turn the immune system on, because it's obviously not working, if that tumor is developing.
So out of that, that's a huge area. If we go specifically to the checkpoint inhibitors, I mean, you can't watch television or a sporting event or pick up a magazine without seeing these direct to consumer advertisements on the human side. So that Keytruda, for example, is probably the one that most people see on television ads every night on the national news or whatever. And, and these are all the, the immune stimulants that take the brakes off the immune system. And it's resulted in even a couple of Nobel Prizes. It kept, you know, former President Jimmy Carter alive for years with advanced stage 4 cancer spread throughout his body. Just phenomenal drugs. The problem is they only work in a minority of patients as a single agent, about 20% of patients. And the other problem from a veterinary standpoint is that these drugs are monoclonal antibodies, and they have to be species specific. So gilvetmab, for example, the USDA conditionally approved agent for dogs, the very first checkpoint monoclonal was canonized. That is that the monoclonal antibody was created to be like a canine. If you don't do that, if you try and use the human agent, the dog's immune system will actually mount an immune attack against that drug. So that's kind of the first step in gilvetmab, which is a Merck animal health product. I mean, who better to make the canine version of Keytruda than the company that made the human version of Keytruda? Now a caveat, I am a key opinion leader, paid the speaker, and for former animal health, I should say that right at the outset. But I'm just talking more about the idea of checkpoint inhibitors. And now they've come into our realm now where we're scrambling on the physician based side and the veterinary based side is how do we take that? 20% of people that are lucky enough to have immunologically hot cancers respond to the checkpoint inhibitors and turn it into the majority of patients, and that involves combination agents and combining things like checkpoint inhibitors with other modalities of cancer treatment: surgery, radiation therapy, etc. And that's really where my research is right now. And, you know, Gilvetmab is kind of the tip of the iceberg. There are multiple kinds of checkpoint inhibitors. And we've been working in the last couple of years on combining those. We now have canonized versions of the Keytruda like drugs, which is a course against something called anti-PD-1. Now we have the other major one, which is an anti CTLA-4. There's a national trial of which we entered the very first case last week of a combination of a canonized anti-PD-1. So a Keytruda like drug and an anti-CTLA-4. In people with advanced metastatic cancers like melanoma. That's the standard of care now. And if we're going to be investigating combinations, you know, adding the standard of care to surgery or radiation therapy, we really need to be at that level. We can't be behind the curve and be able to inform human trials. We have to be ahead of it. So we're looking at those dual checkpoint inhibitors, along with things like surgery and you know, along with things like radiation. It's really changing the paradigm of how and when we treat. For example, in the past we used to say, well, the way to deal with this aggressive tumor is to get the primary out and then start with something systemic. And we now know with some of the immunotherapies, in particular, the checkpoint inhibitors, that the paradigm has to flip. We need to start immunotherapy before doing the surgery or before doing the radiation therapy, because the immune system needs to have that cancer that those antigens, that those targets present to be educated, to go and take off. So most of the trials now involve at least a couple of cycles of the immunotherapy before you do the definitive therapies like surgery and radiation. That's the paradigm that we're helping to shift with our combination trials. So there are certain things that we certainly can do before they can in physician-based oncology. And that start combining therapies. And as I mentioned, one trial that we finished last year that involved combining low dose radiation therapy as an immune stimulant with checkpoint inhibitors has led to a human trial that has just begun with the same agent. So we could do that before they could on the human side. Because the National Cancer Institute realized that we needed checkpoint inhibitors that were canonized in order to inform them on the human side, that funding came in. And now we get that back in our clinic. So that's again, another example of the bi-directional flow. If we can inform on the human side, the funding will be available for us to develop the tools to do it. And ultimately we get it back in our clinics.
Dr. Venable: Now that's great. So I think a lot of times people don't understand how expensive and involved with time and money to do these things. So I'm really excited that there are other groups out there that saw a good opportunity, veterinary medicine, and are helping to provide the funding so that we can really get this research out. And one thing I was wondering, you were saying that we're able to move faster or do some of these studies in veterinary medicine than they are in people. Can you explain why we're able to do more combination therapy and vet medicine versus what they're able to do in people.
Dr. Vail: One, most of our aggressive cancers, there is no standard of care. We haven't been working in the immunotherapy space for very long and as a whole, there are some caveats to that. But if there is no standard of care, we have a little bit more leeway to start combining things before the process to take a new combination therapy into a human clinical trial is phenomenally complex. The rules and regulations. That's not to say that we don't operate under good rules and regulations, but we have to show justification that if an agent is singularly safe, then we have to do small pilot studies to show that the combinations are safe. That's easier to do in our companion species when they have aggressive disease, and there's no good standard treatment that we can start combining those. So we have a little bit more leeway to do that.
Dr. Venable: You know, you were talking about checkpoint inhibitors and how the response rate is pretty low. And generally it seems like we use it in more advanced cases. But when you're talking about using it in a combination role, are you looking at it with still advanced cancers, or are there some earlier stages where we can maybe use these drugs?
Dr. Vail: Yeah, if we have a standard of care that's good for early stage disease. So early stage disease is generally easier to treat, obviously, than late stage disease before it spreads. Then that kind of the more traditional therapies like surgery, radiation therapy may be appropriate. Most of our trials, most of the trials that I'm involved with involve advanced stage disease. That's really where we need to push the envelope. So even today, even with the new immunotherapies, a diagnosis of metastatic disease generally means that it's an incurable disease, that immunotherapies are pushing that envelope dramatically again, as single agents, about a 20% response rate of durable years response in very advanced disease. Now when we start combining things, that's when we start to move to 20% to 40% to 60% to 80%. So that's really where we need to be going. So most of my trials are indeed in advanced disease. Now there are examples where we take local disease and apply these therapies. And those are generally to look at because if we can remove a tumor in total, we can start by looking at the effect of that single agent on a primary tumor and remove it and have that huge bio specimen to look at and see what we would do. So that's an early step as well that can benefit us and certainly benefit our clients, because these studies are generally fully funded. So for example, a dog that presents to us with a, you know, a large oral tumor that our caregiver just doesn't have the financial wherewithal to deal with the clinical trial. Most of our clinical trials will also have additional funding to actually do the definitive therapy, like the surgery or the radiation therapy. So that's kind of a win-win situation.
Dr. Venable: It can help a lot of people. It can help gain our knowledge for dogs, for people. And I love how it could certainly help owners who, you know, maybe financially or other reasons wouldn't be able to do treatment. And now, because of a clinical trial, they're able to help in so many ways as well as helping their pet. So I think that's fantastic. And going back to immunotherapies, what kind of cancers are you finding are good options for these immunotherapy so far?
Dr. Vail: So that, you know, immunotherapies, there are certain tumors that are more likely to respond to immunotherapy than than other tumors. And those are what we kind of term as the immunogenic tumors. So in people, you know, kind of the poster children for immunogenic tumors are malignant melanoma, advanced lung cancer, the urinary tract cancers like bladder cancer. Those are all highly immunogenic tumors. Now there are ways that we can take poorly immunogenic cancers and turn them into what we hope are highly immunogenic cancers. And that's what a lot of our clinical trials try to do right now. That seems to hold fairly true in the canine world. And you know we're talking a lot. I'll just take a step back here.
We're talking a lot about dogs here. Cats. Cats are, you know I often say they're often orphaned in the clinical trial world or the drug development world. And that's really unfortunate. I don't want to suggest that we don't do trials in cats. We do. And as a matter of fact, companies that we're working with right now have active feline checkpoint inhibitors in the pipeline and that we're investigating as well. So, okay, back to where we were.
So yeah, it does appear that melanoma is certainly one that we see responses in. We see responses in squamous cell carcinoma. Head neck is another immunogenic tumor as well. We also have a problem in veterinary and ecology in that the number one predictor of response to immunotherapy, and in particular the checkpoint inhibitors, is the mutational load of that particular cancer. Because the number of mutations in a cancer equals the number of potential targets, because the mutations lead to peptides or proteins that are abnormal that the immune system can recognize something called a neoantigen, of course. And the more neoantigens result from more mutations. So high mutation tumors tend to respond to the checkpoint inhibitors. For example, the Keytruda drug, very effective in a 20% population of one cancer patient, is even more likely to respond if that patient is a smoker. And so are smokers, of course, their tumors have much higher mutational burden because smoking causes mutations. Of course, they wouldn't have probably gotten cancer in the first place if they hadn't been smoking. But if they do develop cancer and they're smokers, they're almost twice as likely to respond to immunotherapy. The checkpoint inhibitors. The problem on the veterinary side is that our companions don't live as long as people do. And the longer you live, the higher the likelihood of mutations developing. And so the higher the mutation load and the more likely you'll respond to immunotherapy. So the canine population to a degree is more like the pediatric human cancer population, in that the tumors tend not to have a really high mutational load. And so immunotherapies are less likely by themselves to be effective. And that's again another reason why we're involved in combination therapies.
Dr. Venable: Yeah. That's interesting. I never really thought about the mutational load. But that does make sense. You know, thinking about a longer lifespan. So how do you go about getting into some of these trials. As I mentioned, I don't think a lot of people really realize how much is involved with doing this kind of thing and getting funding. And so I think it's great that we're getting some more interest in veterinary oncology. And could you just explain, like what to know via what all you had to go through to get that drug to market, to go from the original benchtop clinical research all the way to commercially available.
Dr. Vail: Yeah. So Tanovea was brought to us by a company, an antiviral company, a multi-billion dollar multinational company that primarily worked in the antiviral space. And, but some of the antivirals, because they attack nucleotides and, and nucleic acids, it was determined that there may be an anticancer potential for that drug. And they had a program that was looking at their agents as potential for anticancer. And the one that kind of lit up in their portfolio is kind of a story that illustrates a number of the examples, was a drug that required an enzyme system to after you gave it, it converted it to the active drug. If you gave the active drug to a person or a dog, it was too toxic. They needed to give the drug. It would get into the tumor cell, and then the enzyme system would convert it to kill that. Mice, which is what preclinical researchers often use as a model. Don't have that enzyme. They couldn't convert the drug. Dogs could. That's why they came to us in the first place. So it was kind of a fortuitous thing that brought them to us. And so we could have a look at that particular drug, the resources, the infrastructure and the dollars are there for human cancer research. They're better now on the veterinary side. But back then there wasn't much at all. And there's still, comparatively speaking, not much. So in order for us to do the types of clinical trials, we really need interest on that physician-based side. And an understanding of the importance of a comparative approach to bring that money so that we can run these clinical trials. And that's what this group did. Their pathology department, which was heavily involved with this drug. Most pathology departments in the pharmaceutical area are DVMs. They're veterinarians. because they're also expected to work on preclinical models like mice and rats, etc. And so veterinarians are generally nice people, and they were great to work with. They came to us and so we could communicate on that level as well.
They had some pre-clinical data in laboratory dogs giving us an idea of a sense of dose. And so we started looking at that in our companion dogs with naturally occurring cancers. They were fully funded trials. They paid for the treatment, paid for any adverse events or side effects that occurred. And because they knew their major signal was non-Hodgkin's lymphoma. And we see a ton of non-Hodgkin's lymphoma. Right. I mean, there's probably not a day in your practice that goes by that you don't see at least two lymphomas, right, to non-Hodgkin's lymphoma. So we started treating it, and the results were miraculous, you know, 90% response rates, immediate. Lymphoma is, as you know, a very liquid tumor that comes up quickly, goes away quickly. And at that time, we also had a good working relationship with the medical physics group here at the Human Cancer Center. The University of Wisconsin is world renowned for metaphysics and imaging. And so we started doing pet CT, some of the first pet CT that were done on pet dogs. It's not called a pet CT because it's done on a pet. It's called a PET CT because it's Positron Emission Tomography, of course, but everybody thinks that and we created these beautiful images of a dog before treatment. And five days later, after the agent and the cancer was essentially squashed. And those images we sent to the company and immediately they had interest in this drug and they literally put millions of dollars into the development of those drugs. And again, at the end of the day, we got that drug back and it was very inexpensive for us to go through and get that drug approved because of all the dollars that it had been spent on developing it on the human side. So again, an example of a win win for all species involved in the comparative oncology approach.
Dr. Venable: Yeah, I do love the win-win. That's one of the reasons why I got into veterinary oncology. I love the translational aspect and how we can learn from dogs, but can also help people. So with the Tanovea, is that a drug, do they use it much in people?
Dr. Vail: That class of drugs used a lot. There's many differences in that non-Hodgkin's lymphoma space is a very populated space on the human side. They have, you know, literally a million drugs that they use in different scenarios. So it was a type of drug in a class of drugs that the space had already been filled with. So that's when it was licensed back to the veterinary profession. And then it happens a lot.
Cerenia, the anti-nausea drug, was actually one of the, you know, NK-1 receptor antagonist drugs for anti-nausea, which is the best drug class to use for chemotherapy induced nausea. But in people in their clinical trials, they noted that it was causing a very slight but measurable acute interval prolongation in EKGs. And that's known in people to kill drugs, because that could, in very rare cases, lead to a life threatening arrhythmia. Dogs have a normal sinus arrhythmia. And so it doesn't put them at risk like it does people. So that drug was actually developed by Pfizer. And then given to Pfizer Animal Health, who's now Zoetis, of course, because it was safe in dogs, but there was a really slight risk of a problem in people and so they killed that program. So it's kind of another example of where we gain back from human drug development as well.
Dr. Venable: Yeah. I never knew that with Cerenia. I never heard the back story. But I certainly prescribe it all the time.
Dr. Vail: All the time. Yeah. The whole comparative medicine one medicine approach can really be very, very helpful. And the infrastructure has grown dramatically in the last 20 years. You know, the comparative oncology program now at the National Cancer Institute, that all came out of veterinary work. And the idea that, “Look, if we look at cancer in one species, it'll help another species.” And so that's been very beneficial.
Dr. Venable: So what do you see in the future or in the frontier right now, either bi directional or just in general for veterinary medicine?
Dr. Vail: Yeah, it's kind of you know, it's global. I think immunotherapy from a cancer standpoint is the hottest area. I mean, immunotherapeutic drugs and technologies have, you know, over the last decade have been the, you know, the compound of the year or the, the drug of the year or whatever and all the major meetings. And so right now, the combinations of those with other more traditional therapies is really with the hot areas. And that's certainly what we're looking at. The other area that is very exciting is the prophylactic anti-cancer immunotherapies in. As you know, we've been involved and we're one of three sites that had just completed accrual of the largest interventional anti-cancer clinical trial in the history of veterinary medicine, 900 dogs for a prophylactic anti-cancer vaccine. And the other thing is that it's potentially shovel-ready, off-the-shelf type of thing, so you don't have to personalize it to an individual that cuts down costs, essentially the cost of a flu vaccine. Those are kind of exciting areas looking both on the human and and the veterinary side.
And then the other area that's getting a lot of press as well as, of course, early detection. And there's a lot of that going on right now. It's and the veterinary side is pretty much the wild, wild West. They're very poorly regulated in a lot of strong opinions based on weak data, but there's certainly some potential for us to be able to detect very early some forms of cancer at the level that we're at now, probably the best use of those early tests, like, you know, a drop of blood test or something called a liquid biopsy is to monitor therapy, looking for recurrence rather than a screening test or just not at that that level right now. And, you know, and we often worry, you know, we've been talking about this for the last ten years, these early detection or screening tests. Could it, you know, unfortunately the flip side of that is it would become a euthanasia test? That is that you test for it, it looks like your dog has cancer, but it needs to be so heavily validated. And you have to have an endpoint or an actionable result from that test. Is it something that I can treat? or is it something that I have the finances to treat? Is it, etc., etc.. So there's a lot of ethical movements as well involved in that, but certainly an area of active research that the liquid biopsy or the bio specimen, that early detection biomarker work.
Dr. Venable: I'm definitely excited about all the immunotherapy too. You know, there wasn't much for quite a while, and now I feel like all kinds of things are starting to bubble up. So I'm excited to see how all that's going to come through and what we'll have available for us in vet med. And on the screening tests, I did have a question. You know, you said it's kind of the Wild West, which I would agree, but you mentioned it. It's not so much for people. I know it is much more heavily regulated. Could you kind of explain what is the difference as far as a screening preventative approach between vet med and in human medicine?
Dr. Vail: It's the technology is heavily regulated, especially if you're going to take action based on it. But the results have been less than spectacular from a standpoint of early detection. Early enough, and specific and sensitive enough to be meaningful. And the actionability part of it is really tough. You can look for all these mutations and say, okay, from a blood test to liquid biopsy and say, there's a mutation in this signaling pathway that drives cancer. Well, when you don't know whether it's driving that cancer or not, you just know there's a mutation there. If you can show that it's a driving mutation, then you have to have a drug that targets that, and the drug has to be safe that targets that, and it has to be for the right species, that targets that there's been a and and then you ultimately have to show that. And this is where most of this technology falls apart, is that if you take a liquid biopsy of a patient with this particular disease, and you planned therapy based on the results of that liquid biopsy, is that better than the standard of care? Is that technology actually getting you to a point where you can treat it better? And that's where it's kind of fallen down so far.
I mean, it's not that we shouldn't be looking at, everybody is, trust me, everybody. You go to big meetings nowadays with the American Association for Cancer Research and the American Society for Clinical Oncology, all the clinical trials as part of them, kind of, you know, almost, you know, a sidebar is they're all collecting samples to look for biomarkers. And we do the same thing. All of our clinical trials, we are either collecting, you know, cell free DNA samples or whatever, so that we can, if not immediately, retrospectively, go back and look for biomarkers. So yeah, it's a very active area. Obviously, if we did have sensitive and specific tests, that would tell us early when a tumor is developing and be able to turn on either the immune system or have a drug that would act. The earlier you act, the more durable the outcome is going to be in the higher likelihood of cure. So that's a huge area.
And then the other area that when you look at the proportion of dollars that are spent in the cancer treatment world, the least amount of dollars has been on prevention. And that doesn't make any sense at all. You know, if we can prevent cancer. And so, you know, there's, you know, a whole area of the National Cancer Institute involved in trying to come up with preventative measures. And so, you know, even things as simple as papillomavirus vaccines, you know, that prevent cancer. That's a preventative. But the dollars that go into that, there are political ramifications behind that, unfortunately. They have a drug that's super effective that almost 100% prevents cervical cancer, for example. And they can't get penetrance into certain health care systems because of political events. And I don't want to get all political. So I'm not going to, but I'm just saying that there are all kinds of considerations.
Dr. Venable: Yeah, that is wild how crazy things get the more you dive into it. Right? Like it sounds simple and the more you get in you're like, oh wait, there's a lot more going on here. Well, I really enjoyed this conversation, Dr. Vail, and I've learned so much. It's so exciting. All the different things you're involved with, as well as the span of your career and different influences. I feel like we could definitely do a whole another podcast on multiple topics.
Dr. Vail: Yeah. One thing that we really didn't talk about is that yeah, yeah, I've had a long career, but I've, you know, stood on the shoulders of mentors and my mentees that are going out there are doing amazing things, and it's very gratifying. So this isn't a one person or one group event that's going on. This is a global event that we're trying to beat this devastating disease that unfortunately, the majority of us have to deal with.
Dr. Venable: It definitely takes a team. And along with that, who would you recommend as a good fit for this podcast?
Dr. Vail: I'm sure you've had plenty of names thrown around from a standpoint of cancer. You know, we talk about how some of my former mentees Cheryl London is doing spectacular work. Jessica Lawrence at UC Davis is doing great stuff. Doug Tham, if you haven't already had him on the program, he's a very interesting fellow, with a very broad base of knowledge. These are all really smart people. And there's a few of them out there and it's for sure.
Dr. Venable: These are great people. Thank you so much.
Dr. Vail: Some have, you know, a lot more private practice experience. It could be very interesting. MK Klein, for example. I mean, I still do locums all the time because in academic practice nowadays, there's so many layers between me and my clients and the companions that getting back into a locum and, and seeing 100 cases in two weeks and 100 clients is awesome. So I get the best of both worlds.
Dr. Venable: I love it, I love it, you get a little bit of everything, right? The research, education, getting into clinics. So that's awesome. Well again, Dr. Vail, thank you so much. I really appreciate you doing this podcast.
Dr. Vail: Oh my pleasure. Yeah. Anything we can do in the future, just let us know.
Dr. Venable: Well, that's it for this episode of the Veterinary Cancer Pioneers podcast. If you enjoyed this episode and gained valuable insight, we would be so grateful if you could share our podcast with your friends and colleagues. And it would be even more wonderful if you want to give us a five-star rating, positive review, or any kind of feedback on Apple Podcasts or wherever you listen. The Veterinary Cancer Pioneers Podcast is presented to you by ImpriMed.