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. Learn more at imprimedicine.com. That is imprimedicine.com.
Dr. Venable: Hello and welcome everyone to the podcast. I am so excited! Today we have Dr. Doug Thamm, and honestly, to go over his full bio would take half the podcast. So I'm just going to hit the highlights today. Dr. Thamm is the Stuart Presidential Chair in Oncology and Director of Clinical Research at the Colorado State University Flint Animal Cancer Center. He's authored over 200 publications and 25 book chapters. He's also the co-editor of Withrow and MacEwen’s Small Animal Clinical Oncology, which is basically the grail for veterinary oncology. He’s the Editor-in-Chief of the journal Veterinary and Comparative Oncology, which is also a huge journal in our field. And he’s the President of the Veterinary Cancer Society, so he definitely has his paws on a good leadership role and knows a lot about veterinary oncology right now.
Dr. Venable: He was also the 2023 recipient of the Alan Kelly International Prize in Canine Health from The Kennel Club. So you’ve done so much, Dr. Thamm. I’m so excited to dive in and learn more about your journey, what you all are doing now, and where you think the future is heading. Thank you so much for being with us today.
Dr. Thamm: Oh, my pleasure. Thanks for having me.
Dr. Venable: I always like to start by getting a little bit of background. What got you into veterinary medicine, or more specifically, what got you into veterinary oncology?
Dr. Thamm: I think we all can appreciate these kinds of people, but I grew up being one of those “animal kids.” We had dogs and cats in the house, and I was always bringing home little creepy-crawlies I found outside.
In my early teenage years, I think I maxed out at maybe seven fish tanks plus a pond in the backyard. I was also a little equestrian kid too. I owned a horse in high school and did all that, so I had my feet in large animals, small animals, and exotics basically all through high school.
Honestly, I couldn’t really think of another thing I wanted to do as a career—although I had a little bit of a crisis in high school and college where I thought I was going to do music for a living instead of being a veterinarian.
But then some people talked some sense into me and said, “Hey, you can always be a veterinarian and do music on the side. You can’t really be a musician and do veterinary medicine on the side.” So that kind of made the decision for me. It was just one of those logical things because most of what I did in my spare time had something to do with animals one way or another.
Why oncology is a little bit more interesting. Even as an undergrad, I kind of had the research bug already. I worked in a microbiology research lab through a lot of undergrad, and if I didn’t get into vet school on my first try, I was going to go do graduate work in immunology.
So I always thought the research component of this career would be really cool. I kind of knew I probably wasn’t going to be happy in primary care. Don’t get me wrong—that’s an amazing way to make a living, and the relationships that you build with clients are wonderful. We desperately need those people.
But I was really worried I was going to be bored out of my skull after 45 minutes in primary care practice. I didn’t really know for certain which specialty I wanted, though. Over time I thought I wanted to be a large animal surgeon, then an exotics doc, and all kinds of things.
One of the things that really focused oncology for me was a personal cancer experience I had. After my freshman year of vet school, I was diagnosed with non-Hodgkin’s lymphoma and had to take a year off to get treated for that.
I never want to give people the impression it was a dramatic, life-changing experience where I decided, “I’m going to dedicate my life to curing cancer.” It really wasn’t that kind of story. I went in with about a 97% likelihood of cure based on how I presented, so it was really more of an enormous inconvenience that I had to take this time off and get treated for lymphoma.
But I hadn’t really given oncology much thought before that. That personal experience made me go, “Wait, I’m only through one year of vet school. I haven’t learned anything about oncology yet—I wonder if that’s a thing.” I just started looking into it as a result of this unfortunate event.
Then I realized, “Hey, this is really cool.” It seemed like there were lots and lots of research opportunities specifically in oncology—maybe more than in some other disciplines. So I thought I could scratch my research itch pretty easily if I ended up in oncology. And I don’t know… the rest is history.
Although there was a very brief period in my fourth year where I revisited the fish thing and almost pivoted into fish medicine, but the internship I was trying to finagle didn’t end up working out. And here I am.
Dr. Venable: I feel like, for the veterinary oncology community, I’m glad you didn’t go into fish.
Dr. Thamm: What a loss for the fish community, though, right?
Dr. Venable: You know, I guess so. I don’t know.
Dr. Thamm: I could have been the editor of the Journal of Fish Medicine.
Dr. Venable: I’m sure there are at least a handful of people who would totally read that.
Dr. Thamm: For sure.
Dr. Venable: I’m so sorry you had to go through non-Hodgkin’s lymphoma, but I’m glad it seems like everything went as well as it could for you.
Dr. Thamm: Yeah, I mean, don’t get me wrong—it was a drag. It was a hard ten months. But it’s one of the things that got me where I am, so that’s all right.
Dr. Venable: With your experience—having gone through cancer yourself—how do you feel about the similarities or differences between how we treat animals with cancer and how people are treated? Is there a lot of overlap in the clinical experience, or is it very different?
Dr. Thamm: It’s really neat, actually. One of the things I had an opportunity to do during my residency clinical training was an out-rotation in human oncology. I went back to the University of Pennsylvania, where I was treated, to do that rotation and spent a couple of weeks on various clinics there.
I was really struck by how similar the conversations were with human patients and families compared to the conversations we have with our clients— with one very big, very specific difference: there was no talk about money.
In the human oncology clinic, it’s all about: “What’s treatment going to look like? What are the side effects going to be? How does it work?” And they have the same discussions we do about statistics: “We can’t predict exactly what will happen with an individual patient; all our data are in aggregate.”
But the thing that’s so different is the amount of time we spend talking about money.
I think another big difference is that we do a much deeper dive into explaining the why behind what we do—why we’re ordering a test, why we’re recommending a treatment—because of the financial implications. For better or worse, we have to justify what we’re doing in a way that doesn’t always happen in human medicine, and that allows us to impart more information to our owners, whether they want all of it or not.
We’re trying to help an owner decide how to spend their money, whereas human oncology patients, whether it’s cancer or something else, usually—thankfully—don’t have to think about it in quite the same way. That’s probably the biggest difference I noticed.
Dr. Venable: That is really interesting. I never thought about that aspect, but it makes sense. When I go to my doctor, they never talk to me about prices.
Dr. Thamm: Right, and they probably don’t talk as much about the deep “why” behind each test either. They might talk about it with us a bit more because we’re colleagues—we’re more inclined to ask, just out of curiosity: “Hey, how does that test work? What are you looking for?”
A regular patient probably doesn’t ask those questions. So in day-to-day life, that level of explanation often doesn’t happen, whereas in veterinary medicine, it comes up all the time.
Dr. Venable: Since money doesn’t really come into the conversation the same way in human medicine, do you think we tend to give more options in veterinary medicine? I feel like when I’m talking with new pet owners, I usually give at least two or three options—I always try to give more than one path.
Dr. Thamm: Yeah, that whole concept of “spectrum of care” is something I don’t think comes into play as often on the human side. I think the exception is probably in geriatric care where patients have all these comorbidities and other things going on.
There, you might see more of: “We could do this aggressive thing, or an alternative might be this less aggressive approach, given that you’re in cardiac failure and renal failure and you have diabetes,” and so on.
One of the things I talk to my residents about is that sometimes we get really complicated cases—patients with lymphoma who also have a bunch of other medical problems: unregulated Cushing’s disease, horrible skin, whatever. I’ll say to them, “This is what every oncology patient is like in human medicine.” They’ve all got three or four other comorbidities and three or four other specialists they’re seeing.
So I tell them, “Be glad we don’t see that more often than we do.” That’s another big difference: there are usually so many other things wrong with human oncology patients that the medical team is trying to manage. We don’t encounter that as frequently.
Dr. Venable: I hadn’t thought about that either, but you’re right. Because it tends to be older people with cancer, they probably do have a lot of comorbidities. I’m glad many of our animal patients don’t have that same level of complexity.
Speaking of people, you’ve done a lot of research in comparative oncology—using dogs as models for human cancer. What are some of the most interesting or exciting comparative examples you’ve worked on between people and dogs?
Dr. Thamm: I guess there’s one older example that comes to mind, and then a newer one where the jury is still out on how comparative it will be.
One of the coolest older ones was work we did with ibrutinib, which is a small-molecule inhibitor of a kinase called BTK. People are starting to use it in veterinary oncology these days to treat B-cell lymphoma.
About 12 or 14 years ago, we started looking at it as a therapy for dogs with lymphoma in conjunction with this little startup company from the Bay Area called Pharmacyclics, which was trying to develop it as a human drug at that time.
The main question we were trying to answer wasn’t really “Does it work?” so much as it was: “Can we develop an assay to know if the drug is actually sticking to its target in cells?” They wanted to know if they could reliably look in the blood to understand what was going on in the tumor tissue.
People don’t mind having their blood drawn, but they really don’t like having biopsies taken from lymph nodes when they have lymphoma. So we did both in dogs—we looked in the lymph nodes and in the blood, and asked, “Are the assay results similar in both?”
And they were. So we could say, “You can probably just look in the blood of your human cancer patients and feel pretty comfortable that the same thing is happening in their lymphoma tissue.”
The added benefit was that three out of eight dogs in that first part of the study actually had partial responses to the drug, which was very unexpected. On the human side, ibrutinib mostly works really well for the indolent lymphomas by itself.
We don’t see that many indolent B-cell lymphomas in our patients; these dogs had typical high-grade multicentric lymphomas. The fact that we saw any activity at all was pretty exciting in retrospect.
I’m not going to say our results were the make-or-break data that “rescued” this drug from the trash can. But I do think the fact that this small company could go to human investigators and show data from dogs with spontaneous B-cell lymphoma helped get it into human clinical trials faster.
A lot of human lymphoma clinicians may have a choice between three or four clinical trials, and they have to decide which one to dedicate their resources to. I think the fact that Pharmacyclics came to the table with real clinical data in dogs probably got some people more excited than they otherwise would have been.
Now, ibrutinib is a multi-billion-dollar drug, and I like to think that dogs had at least a little bit to do with getting it there a bit faster—which is kind of cool.
The newer example I’m excited about is work that Steve Dow and Dan Regan have been doing to repurpose the blood pressure drug losartan as a cancer therapeutic, specifically because of its ability to interfere with monocyte migration into tumor tissue. I think you’ve had Steve on the podcast, so you’ve probably talked about that.
It’s really cool that we’ve found this new way to use an old drug that might end up being effective in a completely different way than originally intended. We’re excited that this observation is trickling into the human side too.
There’s a study in pediatric osteosarcoma going on right now looking at a combination of high-dose losartan with Sutent, which is kind of like the human version of Palladia, specifically in patients with metastatic osteosarcoma. Time will tell how well the observations made in dogs translate there, but that’s a newer example we’re fired up about.
Dr. Venable: I think that’s really exciting—the repurposing of old drugs. I’m kind of thrifty by nature, so I love the idea of re-using things. But I also feel like for our clients it makes treatments more feasible. Some of the new drugs are just crazy expensive, but something like losartan is very affordable.
Dr. Thamm: Exactly. And on the human side, it’s the same idea, but the savings are at a different level. If it costs $10 million to develop a repurposed drug versus $800 million to develop a brand-new drug, those cost savings are going to trickle down to the healthcare system—even if not all the way to the individual patient.
So, no matter how you slice it, repurposing has real value.
Dr. Venable: Right. And as you mentioned, the numbers can be astronomical. I think people don’t often understand how much it costs to get a drug all the way through the process—from discovery to the point where you can actually prescribe it.
You’ve been very involved with Tanovea. Can you walk us through what that process is like? I think most people have no idea how much is involved.
Dr. Thamm: Tanovea is a neat example because that also started with a human pharma collaboration. About 12–14 years ago, we were approached by Gilead Sciences. They had this molecule they were interested in for people, but because of some oddities about the prodrug (GS-9219), it falls apart in rodent plasma.
So they couldn’t use their typical mouse models of lymphoma to test efficacy. They were scratching their heads going, “How are we going to figure out if this works? We can’t just move forward into people without any preclinical efficacy data.”
The person running the program was a veterinary pathologist named Dan Thomas—funny side note: his daughter is now one of our oncology technicians. Dan said, “When I was a pathology resident at Georgia, we saw dog lymphoma all the time. What if we tried this drug in dogs with lymphoma?”
He reached out to me and to David Vail when he was still here, and we started collaborations looking at Tanovea. At the time, the goal was to make it a human drug. Things happened on the human side that we’re not privy to, and they decided not to keep developing it for people.
So for a while, it just sat on a shelf.
Around that time, a guy named Terry Opgenorth came in to work with CSU Ventures—our discovery and commercialization office. He had been an executive at Abbott Labs (now AbbVie), one of the big pharma companies.
He came in to consult and help run commercialization efforts and ended up so interested in this whole “dog oncology” concept that he started a little company called VetDC. He had friends and colleagues at Gilead, and through some back-channel conversations, he asked, “What would you think about licensing the veterinary rights, since you’re not doing anything with it?”
They said, “Sure, that sounds fine.” They never would have said that to me directly, but because he knew the right people to ask, he got it done.
As a result, we were able to get not only the rights to develop it as a dog drug, but an astronomical amount of work that had already been done on the molecule in preparation for human development—chemistry, manufacturing, reams of safety data, and so forth.
All of that could be repurposed into the application that eventually went to the FDA for conditional approval. All the data that went into the conditional approval—safety and efficacy data for the label—were generated back when we were working with Gilead.
The only piece we had to redo from scratch was the chemistry, manufacturing, and controls: how we’re going to make it, who’s going to make it, how we know it’s the same every time. That was a huge pain in the butt, but at least we had a cookbook to work from because someone else had already done it.
So we had to redo it, but we were using someone else’s cookbook instead of starting from scratch. That probably amounted to 8–10 million dollars’ worth of savings.
Once that was done, the only thing left, officially, to get full approval was the FDA registration trial—the randomized, placebo-controlled prospective trial we published in 2021 or 2022 that led to full approval.
I think the smartest move VetDC made along the way was doing a lot of additional studies—not just that single registration trial. They funded or supported multiple studies, some with full support and some essentially at the cost of drug only.
By the time of full approval, there were around eight peer-reviewed publications on Tanovea: how to use it, what groups of patients it’s good for, how well it works, what to watch for. VetDC came to the table with a substantial portfolio of peer-reviewed data. That really helped clinicians understand it and feel more comfortable early on, instead of saying, “All we have is the label, and none of this has been peer reviewed yet.”
I’m really happy VetDC was so excited about generating knowledge and getting it out there—even before they had a product on the market. We were very fortunate with who was helping us and the information we already had going into development.
Again, everyone involved was excited about doing the science and generating knowledge to help people know how to use the drug.
Dr. Venable: How long would you say that whole process took?
Dr. Thamm: From the first time we put it into a dog to full approval was about 12 years.
Dr. Venable: That’s long, right? I feel like a lot of people don’t realize how much data and time go into this. Do you have a sense of what it would cost, roughly, to get something like that approved from scratch?
Dr. Thamm: If we’d had to start from scratch—without all the information from Gilead that shortened the process—I think on the veterinary side you’re easily looking at, conservatively, 8–10 million dollars. And that’s a tiny fraction of what it would cost on the human side.
But when you think about that cost and the fact that you’re probably only making a few million dollars in revenue per year from these veterinary oncology drugs—especially the ones used mostly by specialists—it makes a little more sense why they have to charge what they do.
They really aren’t making that much money, and it costs a lot, by veterinary standards, to get the drug to market. That’s why, more and more these days, for purely financial reasons, a lot of companies are saying, “We can’t afford to develop a drug that will only be used by oncology specialists.” They just can’t make their money back on something used by 500 people.
So increasingly they’re looking for drugs—immunotherapies, biologics, orals—that can at least partially be used by non-specialists, don’t require special handling to use safely, and maybe can treat multiple types of cancer. Those are the factors guiding big-pharma decisions now: “Is this going to be used beyond people with DACVIM after their name?”
Dr. Venable: You make a good point about ROI—what kind of return they’re getting.
Have you found that, in some comparative studies, where we study a drug meant for human medicine in animals with naturally occurring cancer and then it goes into human medicine—does it ever come back as a dog drug? Or is separate licensure too big a barrier?
Dr. Thamm: I know there are some examples where people hope that will happen. Masitinib (Masivet), which is approved in the EU for mast cell tumors, is one where they’re still pursuing human clinical development. They’re working on that.
But I’m not aware of a case where there’s a human drug and the exact same molecule is also successfully marketed for animals. One thing that makes companies gun-shy is the perception of differential pricing.
From the human-side perspective: “Why should I pay $80,000 a month for a drug you’re selling on the veterinary market for $800 a month?” There’s an old example that caused a lot of problems.
Back in the ’70s or ’80s, it was discovered that levamisole—a cattle dewormer—was a potent immunomodulator. It was used as an adjuvant chemotherapy for colon cancer in humans. They developed and sold it as an oncology drug for humans, but at the same time, you could buy levamisole in 55-gallon drums at the feed store.
Human patient advocates understandably went crazy: “You’re charging us thousands of dollars for something we can buy at the feed store for a fraction of the price.”
That kind of case made a lot of people wary about marketing the same drug at vastly different prices for human and veterinary indications. I haven’t yet seen a modern example of it done successfully, but time will tell.
Dr. Venable: Even with Palladia—the other human drug was sunitinib, right? Would you say they’re still different enough chemically that it’s not the same scenario?
Dr. Thamm: Yeah, they’re different chemical entities. They only differ by a single bond, but anyone who looks can say, “Yes, they’re different.” They definitely pass the “smell test” as separate molecules.
Dr. Venable: The other thing you bring up about cost differentials—I’ve had physicians say, “Well, the chemo we give to people is different than what you give to dogs.” But as far as I’m aware, it’s the same drugs, right? It’s not a different grade. The doxorubicin we give is the same they give to people, correct?
Dr. Thamm: For the older generics, absolutely—it’s the same. And the cost structure is exactly the same.
It’s when drugs are still on patent and companies can charge what they want that the big issues come up. That’s why in veterinary medicine we’re often limited to generics.
Now there’s also compounding, which is very much “caveat emptor.” You don’t always know where those drugs are coming from or whether they’re truly USP pharmaceutical grade.
Dr. Venable: And as far as I know, there’s not an easy way to get detailed information on compounded products. Can you ask a compounding pharmacy for more details about their drugs? I’ve never tried.
Dr. Thamm: You might be able to ask, “Where are you getting your raw drugs from?” but I don’t know whether they’ll actually give you that information.
Dr. Venable: Or ask about third-party testing. With supplements, that’s a big issue—no real oversight and what’s on the label isn’t always what’s in the bottle. I’d think compounding pharmacies have more oversight than supplement manufacturers, but I’ve heard you can ask for third-party inspection reports for some supplements. I’ve never done it; I was curious if you knew anything about that for compounding pharmacies.
Dr. Thamm: I think it varies by compounding pharmacy. Some of them will do more robust quality control—maybe via third parties, maybe internally. Obviously, they aren’t testing every single pill, or they wouldn’t have any pills left, so it has to be batch-based or intermittent.
I do think that’s a legitimate question when you’re deciding which compounding pharmacy to use: What kind of quality assurance do you have in place? Who’s doing it? How frequently? How do you know the amount you say is in the pill is actually in the pill?
Those are great questions to ask when you’re choosing a compounding pharmacy.
Dr. Venable: Another thing we’ve seen in recent decades is different types of products coming out with different regulatory paths. There’s USDA-approved and FDA-approved, and I think a lot of veterinarians don’t really know the difference.
If a product says it’s USDA-approved, what does that mean in terms of the process? Tanovea had to go through the FDA, correct?
Dr. Thamm: Correct. USDA only has authority over biologics—vaccines and some antibodies. Theoretically, if there’s a cell-based therapy, that might go through USDA as well.
Drugs are under the purview of the FDA, the Food and Drug Administration. That’s the basic split.
It gets a little confusing in the cancer therapeutics market. All cancer vaccines go to USDA. Any cell therapeutics—a cell-based vaccine, activated immune cells, etc.—would also go to USDA.
Where it gets really weird is monoclonal antibodies. If you have an antibody that works mostly by engaging the immune system—like a checkpoint inhibitor—that goes to USDA. If you have an antibody that doesn’t primarily work that way—for example, one that blocks a receptor–ligand interaction, like Librela (nerve growth factor antibody)—that goes to FDA.
So if you can, with a straight face, say “This works by engaging the immune system,” you’re probably going to USDA. If the answer is no, you’re probably going to FDA.
Regardless of which agency, you still have to answer three big questions: Is it safe? Can you reliably manufacture it? Does it work? Those are the same three pillars whether it’s USDA or FDA—but the specific rules, how you prove each pillar, timelines, and costs all differ.
There are specialized consultants for each agency—some people only work with USDA, some only with FDA. It’s a bit arbitrary how some of those lines are drawn, but that’s the lay of the land.
Dr. Venable: With USDA, is the approval process as strict or as expensive as FDA?
Dr. Thamm: It kind of depends on the era. USDA has swung back and forth between being pretty lax and being really stringent, and then back again—depending on… I don’t even know what. The political or regulatory “flavor of the month,” maybe.
So it depends who you ask and when, as to whether things are easier, harder, or about the same between the two agencies.
Dr. Venable: When I’ve looked into some of this through consulting, it’s been interesting to see who does what.
Another thing we’ve seen recently is new diagnostics in veterinary medicine. As I understand it, many veterinary diagnostics don’t have to apply for formal approval. Is that correct? In human medicine, do diagnostics have to go through FDA or USDA?
Dr. Thamm: On the veterinary side, diagnostics are completely unregulated. It’s the Wild West—buyer beware. Pretty much anyone can hang out a shingle and start selling a diagnostic test out of their basement.
On the human side, the biggest issue is whether the test will be covered by insurance. If it’s going to be reimbursed, insurers want a high level of evidence that it improves outcomes or they won’t cover it. So while that’s not a regulatory bar, it is an evidence bar.
There’s also CLIA, which is a laboratory certification. That’s more about whether test results are reliable and repeatable—not whether the test improves patient outcomes. That’s one bar diagnostics can meet, but again, a lot of it is driven by insurers.
Dr. Venable: So in veterinary medicine, it’s really up to veterinarians—it’s buyer beware—whether a product is successful or not.
Dr. Thamm: Pretty much.
Dr. Venable: You’re involved in a lot of high-level things in vet oncology—journal editorship, VCS leadership. What are some exciting things you see coming up, and maybe on the flip side, some things that concern you?
Dr. Thamm: The thing I’m looking forward to most is seeing more biologics—monoclonal antibodies and related therapies—enter our space over the next few years.
We already have peer-reviewed publications about anti-CD20 antibodies that Elanco has been working on. At the most recent VCS meeting, Zoetis talked about a CD20 antibody they have. Merck has a monoclonal checkpoint inhibitor out there. There are other checkpoint inhibitors in development. Zoetis has the nerve growth factor antibody Librela.
I think we’re entering the era human oncology entered about 20 years ago with monoclonal antibodies. It’s becoming much easier, thanks to molecular biology tools, to develop and ultimately produce these antibodies at scale.
I’m hopeful that in the next 5–10 years we’ll see more antibodies become available. And the “naked” antibody—a simple monoclonal antibody in a vial—may just be the tip of the iceberg.
The next step is bispecific antibodies. Remember from basic immunology that antibodies look like little “Y” shapes. The top two arms recognize things and the stem interacts with other cells. Bispecific antibodies are engineered so one arm recognizes your cell of interest (like a tumor cell) and the other arm stimulates the immune system—perhaps by engaging T cells.
On the human side, so-called bispecific T-cell engagers are really cool. They let you target a cancer cell and activate T cells at the same time. It might be a way to do something similar to CAR-T, but with an off-the-shelf product in a vial that we could give quickly in practice.
That would be really exciting if people start designing those for dogs.
One concern is that bispecifics may be more toxic than naked antibodies. Whether companies and the vet oncology community will be comfortable marketing those broadly—beyond specialists—will be interesting to see. We’re not going to know how toxic they are, or how hard they are to manage, until we try them.
I’m also very excited about how cheap DNA sequencing has become. We’re learning a lot about what dog tumors look like genomically and how similar or different they are from human tumors. That’s incredibly exciting—but also a double-edged sword.
We know how to sequence DNA now, and I certainly believe the people doing it. The problematic part is over-extrapolating from human data, which isn’t even the same from tumor type to tumor type.
Just because a tumor has mutation X doesn’t mean we should treat it with drug Y. That might be true for some cancers and completely untrue for others. We don’t know any of that yet.
So just because we know how to find mutations doesn’t mean we know what to do with them. That’s going to be a much harder problem to solve than sequencing. And the only way we’re going to figure it out is one drug and one mutation at a time.
That’s long, complicated, and expensive. I don’t see another way, though.
Dr. Venable: Is anyone running clinical trials along those lines now? Are you doing any trials that integrate genetic sequencing or precision medicine?
Dr. Thamm: We’re doing a lot of sequencing, but not yet with an eye toward true personalized medicine because we’re not there.
We just finished—or are finishing—a study looking at single-dose plasma pharmacokinetics for some targeted agents people are starting to use. For a lot of the drugs being used clinically, we don’t even know if we can get enough into a patient to do any good.
We’re trying to crack that problem a bit: if people are going to use these drugs, let’s at least take a stab at whether we can reach therapeutic exposures.
We’ll eventually publish that data so people know, “If I reach for this drug, do I have any realistic hope of getting enough into a dog to be helpful?”
But we’re nowhere close to saying, “If a dog has this mutation, give that drug.” We’re not there. We have to figure out the drug side first.
In parallel, we’re sequencing a lot of dog tumors here. Anne Avery and others have been doing that for years. But putting the genomic data and the drug-response data together is where it gets really tricky.
Dr. Venable: So the hard part is figuring out, “Is this mutation actually a driver, and will this specific drug work with it?”
Dr. Thamm: Exactly. You can find a mutation that’s clearly a driver for one cancer and not for another.
The best human example I can think of is BRAF. It’s an unequivocal driver mutation in human malignant melanoma, and drugs like vemurafenib work great there.
But you can also find BRAF mutations in human thyroid and colon cancer, and vemurafenib doesn’t do anything in those settings. Same mutation, same drug, completely different outcomes.
How are we ever going to figure that out across multiple cancers and species? It’s going to be tough.
Dr. Venable: It definitely sounds like an uphill climb. And like you mentioned earlier, there’s also the dosing piece—you have to know whether you can even get enough drug into the patient. That made me think of the losartan work, where they found we had to give way higher doses than you’d use for typical blood-pressure control.
Dr. Thamm: That’s a really excellent example. If Steve Dow had just said, “Losartan affects monocyte migration—let’s use the regular dog dose,” without looking at the PK/PD, we’d have given ten times too little and it would have been a negative study. The idea would have died there.
Without that informative PK work, you never truly know if what you’re doing has any chance of working.
Dr. Venable: It’s one I think about a lot because, I don’t know about you, but often when I prescribe high-dose losartan, pharmacists freak out. They tell owners, “This is lethal, don’t give this,” and I have to reassure them it’s okay.
Dr. Thamm: Yeah, we’ve had the same thing happen live.
Dr. Venable: I guess the positive is that the pharmacist is paying attention, right?
Dr. Thamm: Totally.
Dr. Venable: Another “future-facing” area is precision medicine and data-driven approaches like AI tools. How do you see those fitting into oncology or even veterinary medicine in general? AI is such a big topic right now.
Dr. Thamm: That’s a really interesting question. A colleague of mine is actually trying to determine if there’s enough interest for a standalone journal on artificial intelligence in veterinary medicine—not just oncology, but across the field.
The fact that this is even being discussed shows how much activity there is.
In our day-to-day practice, we’re already using AI to abstract medical records. When we get referral records, we have AI tools—officially sanctioned by the veterinary teaching hospital—that we can use to extract summaries so people don’t have to wade through 120-page PDFs.
We’re also starting to use AI-based dictation tools for case summaries and such, at least in exploratory fashion. That’s already here in the clinic, which is pretty exciting.
Some of the other low-hanging fruit will be AI-based tools for blood smear review and cytology. There are companies out there already marketing those. I think we’ll also see more AI services for radiograph interpretation. I’ve only encountered those a couple of times, and so far I haven’t been super impressed—but they’ll get better.
The things that worry me are the “black box” nature of these tools. Nobody really knows what the models are “thinking” or how they reach their conclusions. In medicine, that’s scary.
One of the things I love about looking at a cytology or a radiograph with a pathologist or radiologist is that you can walk down the hall and ask, “Why did you say this is lymphoma and not reactive? Can you show me?”
They’ll pull up the slide and talk you through it. You can’t do that with AI—you just have to trust it.
That’s scary for a lot of clinicians. We might end up in a situation where there isn’t a human professional you can call to explain the why behind a decision.
On the therapeutic or personalized-medicine side, there’s also the question of how much control we’re willing to hand over to algorithms. To what extent are we going to let a machine make the final decision for a patient?
That may end up being generational. As people grow up with AI integrated into daily life, they might say, “Of course an AI is reading my radiographs, who else would do it?” For those of us who are older, we’re more like, “Wait a second, I’m not sure how comfortable I am with that.”
So we’ll see. It’s a super interesting space, and I’m really curious what the next 5–10 years are going to look like.
Dr. Venable: I think it really will move that fast. In 10–15 years we could see big changes.
It’s funny you mention generational differences. I’ve worked with clinics that fought against fax machines, then really fought against email. Does that mean I’m going to be the one fighting AI? I don’t know—maybe.
Dr. Thamm: It’s totally true. AI is coming really fast, and I hate to say it, but it’ll probably be here before we’re ready—not just in medicine, but across society.
We’re not going to quite know what to do with it for a while. The technology will likely be here before the wisdom about how to use it well.
I’m not saying it’s going to take over everything and destroy humanity, but there is a real worry that we’ll let it do more than we should and end up making some bad decisions as a result.
Dr. Venable: Hopefully enough people keep raising those issues and asking about oversight so it doesn’t turn into the Terminator movies and we’re okay.
This has been great. I always love chatting with you. It’s so fun to catch up. I know it’s been more than a hot minute since you were my mentor at Colorado, but it’s so great to see you.
As we wrap up, I always like to ask: who do you think would be a good person to have on this podcast?
Dr. Thamm: I think a really interesting person who could speak to the clinical side and what it’s like running a big, extremely busy, and complicated academic oncology service would be our own fearless leader, Dr. Sue Lana. I think getting her insights would be really cool.
Dr. Venable: That’s a great suggestion, because it’s a different angle. You all certainly run a huge service. CSU is very well known, and you’ve done a great job of keeping that reputation. It’s not like, “This was the university for a few years and then faded.” You’ve kept the bar high and kept it there, which I’m sure is not easy. She would be great to talk to, for sure. Well, again, Dr. Thamm, thank you so much. I really appreciate having you on the show today.
Dr. Thamm: Thanks, Dr. Venable. Great to talk to you.
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.