Guannan Wang (00:01)
Hello everybody. Welcome to another episode of the VetOmics podcast, Genomic Diagnostics and Precision Medicine in Veterinary Oncology. I'm Dr. Guanan Wang. I'm a genomic scientist and a founder of VetOmics.

We are a company dedicated to delivering best-in-class, high-clinically actionable genomic tests for pets with cancer. As we all know, precision medicine has transformed human oncology. But in veterinary medicine, we still face gaps in genomic data, drug use information, and access to newer...

better class targeted and immunotherapies.

Our mission at Vetomics is to help close this gap by generating better data, advancing education, and working with key stakeholders to bring practical, effective precision oncology to our furry family members. Today, I'm so thrilled to be joined by Dr. Janet Carreras a board certified Veterinary Oncologist whose career

beautifully reflects her passion for people, pets, and science. Dr. Carreras attended the College of the Holy Cross in Worcester, Massachusetts, where she received her bachelor degree with honors in chemistry in 1993. Chemistry, that's very interesting.

Janet Carreras (01:44)
Good.

Guannan Wang (01:47)
Dr. Carerras earned her VMD from the University of Pennsylvania, where she also completed her internship and residency. She spent 14 years as an oncologist at the Gulf Coast Veterinary Specialist in Houston, Texas, and later worked with IDEXX providing expert oncology consultations to veterinarians across the country.

In 2021, Dr. Carreras returned to the clinic where she joined Piper Veterinary in Middletown, Connecticut. These experiences have shaped her compassionate and curiosity-driven approach to care.

Dr. Carreras is one of the early adopters of genomic testing and genomic guided cancer management. And she is always going above and beyond to find new ways to help her patients, many of whom are battling aggressive metastatic cancers. ⁓

Dr. Carreras thank you so much for being here today. Would you like to share a few words before we dive into some of the topics I'm so excited to discuss with you?

Janet Carreras (03:09)
Yes,

I just I really want to say thank you for inviting me to be on this podcast with you. I am such a supporter of everything that you do that makes ⁓ our ability to treat our patients really so much better. And I know that you have been working really hard and have really dedicated yourself to make this available to our canine and excitingly now.

Guannan Wang (03:38)
Yeah.

Janet Carreras (03:39)
feline patients now

I just feel ⁓ so excited about where we are in veterinary medicine. It's like a whole

The flood gates have opened and we have so many more tools in our tool shed. It's really incredible ⁓ to be a part of that. It's really exciting and fun at this point in my career to be like, wow, everything's changing. Yay. You know, so awesome. Really, really, really, really neat.

Guannan Wang (04:04)
Yeah.

Perfect, yeah. So I heard some doctors said that, ⁓ because now we have this, I cannot retire anymore. So I assume the same applies to you. You can't retire because we have so much. Yeah, exactly. Yeah. ⁓

Janet Carreras (04:20)
⁓ Yeah, right? I'm not going to be able to retire anyway, but I'm not only kidding. It is. It's really, yeah, this is really

funny. So I worked in Houston, Texas, and ⁓ at one point, I don't know, anybody from Houston, Texas might recognize the name Marvin Zendler, but he was a...

like on TV, what are those people called? Like a reporter on TV and he was really famous. And I remember he asked me at one point during an interview, you know, what are the big changes in veterinary oncology? And I was like stumped. I was like, I guess, you know, there weren't. And that was the really hard.

hard thing to kind of come to terms with. So it's really ⁓ amazing to see what really has changed over the last few years and it's exciting. So thank you. Yeah.

Guannan Wang (05:15)
Very exciting.

We're only scratching the surface, but we already see so much promise and so much good data. So we'll continue to fight the good fight. All right. I'm going to dive into my questions. So these set of questions I ask many of our doctors, but each time I just learn something new. So I'm really excited that we get to see your

Janet Carreras (05:27)
Yes.

Guannan Wang (05:44)
experience and what your perspective and how do you handle all these ⁓ not everything is perfect and a lot ⁓ of hurdles how do we overcome that so love to learn that okay all right the first set of questions is decision making in recommending genomic testing so for how many patients how many new patients do you see every week

Janet Carreras (05:59)
you

say typically anywhere from 6 to 12 and probably normally about 8 to 10. It's pretty typical.

Guannan Wang (06:20)
Okay, okay. That seems, like pretty typical. That's a lot also, new patients besides managing all the other patients. So, like, do you recommend genomic testing to all of them? And how do you make that decision?

Janet Carreras (06:38)
I would say more and more I do. Some of it has to do with, you know, there's gonna be some that are like a soft tissue sarcoma that's probably cured with surgery and, I don't need to. But more and more I do recommend it when I really, so some of it might be that I know that conventional chemotherapy just isn't that effective. And so I'm really looking for something

Guannan Wang (06:52)
Mm-hmm.

Janet Carreras (07:08)
that might be more effective for a given patient. ⁓ And more and more it's based on experiences that I've had or heard others have with targeted therapy. ⁓

Also, you know, there are certain times that, you know, you are recommending conventional chemotherapy in conjunction with targeted therapy. So ⁓ that's really valuable as well. ⁓ There's a lot to get out of that initial ⁓ report. So yeah, you'd be surprised, Guannan, almost every time.

Guannan Wang (07:32)
Mm-hmm. Yeah.

Wow

that's that's you know actually so humbling to hear I think that you are ⁓

the first one that says that you recommend for most of your patients and that you send in a lot of cases hopefully this is a trend that we'll see more and more. And at the end of the day, we hope that these tests or the genomic guided treatment actually bring value, bring benefit. That's the ultimate ⁓ test, right? So we'll have to,

continue to collect data So that's so good to hear. So that's literally like a practice change, right? Now that you incorporate genomics in almost all of your new patients, or at least you'd like to. So that, you know, whether the owner decide to do it or not, that's another question that we'll get back to later. Yeah.

so basically for cancers that you know the standard care of therapy may or may not work so you definitely recommend, but for some cancers ⁓ like grade one soft tissue sarcoma you know that surgery is basically the cure and then so for these cases that you don't

recommend genomic right away. So that's very interesting. so I recently had a conversation. was so curious because a lot, we see a lot of soft tissue sarcomas.

Janet Carreras (09:22)
Mm-hmm.

Guannan Wang (09:22)
but almost all of them are recurrent soft tissue sarcoma. And they always started off as grade one. But when they recur, and they actually become grade two or higher grade. So I was asking, so can soft tissue sarcoma's grade increase over time? So I was told that,

Janet Carreras (09:28)
Mm-hmm.

Guannan Wang (09:50)
We are seeing a ⁓ disproportion of that increasing grade of soft tissue sarcoma because most of the soft tissue sarcoma, they stay as grade one. But then some, they do increase. They do become more and more aggressive over time. And I guess that's the portion that we see a lot. Is that aligned with your experience?

Janet Carreras (10:12)
Mm-hmm.

Right.

mean, I think many soft tissue sarcomas are cured surgically, right? And the standard of care is, you know, local disease management, right? So radiation therapy, potentially electrochemotherapy. I do have a couple of ⁓ patients that are on targeted therapy for incompletely excised soft tissue sarcomas. ⁓ But I think

Guannan Wang (10:24)
Yeah.

Mm-hmm.

as a maintenance.

Okay, ⁓

Janet Carreras (10:45)
As a maintenance that for whatever reason they elected, know, they didn't we don't actually have radiation

therapy in the state of Connecticut. You can believe it. So it's not terribly convenient for my clients to always ⁓ choose radiation therapy. Many of them do, but they do have to go out of state to get it right now. So, ⁓ you know, you have older clients, you have older patients, you have lots of reasons, you know, that they might do something different. So ⁓ that I have

Guannan Wang (10:58)
you

Mm-hmm.

Mmm.

Mm.

Janet Carreras (11:15)
⁓ one at least one patient that's very successfully receiving targeted therapy for an incompletely excised soft tissue sarcoma, you know, it wasn't recurrent or anything like that, but it just was in completely excised.

Guannan Wang (11:28)
Okay, okay, okay.

And it's still like, how long do you keep them on target therapy? I know this is only a few for a few patients.

Janet Carreras (11:42)
Well, that's one of the best questions I know. I think I'm learning about that every day. think

the, you know, a lot of the tumor types that we're treating are really aggressive. And...

Guannan Wang (11:56)
Yeah.

Janet Carreras (11:57)
I never really know the answer to that question. ⁓ I was actually asking someone at VCS about gilvetmab because a lot of the studies are they gave four doses and I'm like, how many are we supposed to give? You know, and I don't think they know the answer to that question. Yeah, most of the time I keep them on it long term. ⁓ But again, I think a lot of the reason for that is because a lot of these things are aggressive. ⁓

Guannan Wang (12:05)
Mm-hmm. Mm-hmm.

Exactly.

Mm-hmm.

Yeah.

Janet Carreras (12:27)
I have a couple of lung tumor patients, metastatic lung tumor patients that have come off of targeted therapy and have been in remission for a window of time. It was wild, you know? So yeah, it is, you know? And you're kind of like, this was metastatic. When am I supposed to stop this? And it's hard, scary.

Guannan Wang (12:33)
Mm-hmm.

That's amazing, right? Yeah. Yeah.

Sometimes it's... yeah, the effectiveness is so... it's surprising. That's the word that I heard. It's so impressive and surprising. And we're hearing more and more.

Janet Carreras (13:00)
Mm-hmm. Yes.

Guannan Wang (13:07)
of these stories, long term remission and to a point that the doctors don't know when to stop. Yeah, and I've heard that people put olaparib as maintenance for over a year or two years, the dog is doing completely fine and...

Janet Carreras (13:16)
And I need to...

Guannan Wang (13:27)
just to keep doing the oral olaparib everyday. yeah, yeah. So at one point, we'll need to figure out, okay, when to stop. So it's the, because as cancer becomes so common and almost sometimes, I think there's a trend to also become a chronical disease, there's a management, okay. So like, you manage the previous cancer now that it's like a

Janet Carreras (13:36)
Yeah.

Guannan Wang (13:57)
three years out. Is the cancer now a new cancer or a ⁓ previous cancer recurrence? So I think at one point we'll have to tackle those questions. But those are all pretty solvable problems or answerable.

Janet Carreras (13:59)
Mm-hmm.

Yeah, have a couple of patients,

it's interesting, that had to come off of targeted therapy because of toxicity, ⁓ who had really good responses ⁓ and have maintained them for a durable window of time. So definitely speaking to what you're saying that maybe really shouldn't keep them on them so long. ⁓ I have a mammary...

Guannan Wang (14:24)
Mmm. Yeah.

Mm-hmm. Mm-hmm.

Mm-hmm.

Okay.

Janet Carreras (14:42)
⁓ metastatic mammary carcinoma that was on sorafenib She had a couple of pulmonary nodules and she came off of it because she was a GI disaster to begin with and loves to eat things and make herself get in trouble. ⁓ So she came off and she is still nothing on her chest x-rays, which is pretty wild. Yeah. So it's a really good question.

Guannan Wang (14:45)
Mm-hmm.

Mmm.

Janet Carreras (15:12)
in.

Guannan Wang (15:12)
Yeah,

yeah, always curious that you know, like there's no standard right? That's why you know, we're hoping to bring some at least, consensus protocols among the doctors, At the beginning or in previous years, everyone is kind of sort of having to figure this out. So we're hoping to bring them like it's like I call it a crowdsourcing effort. So everyone contribute

Janet Carreras (15:17)
Yes.

Yes.

Guannan Wang (15:36)
everyone

you know share your experience so that we can all learn from it. that's great okay all right have you had cases that you recommend genomic testing but then the pet owners decide not to proceed so in those cases what are the main

Janet Carreras (15:42)
Mm-hmm.

Guannan Wang (16:00)
main barriers, ⁓ cost, like treatment complexity, lack of data, so all of the above. What do you think of your experience?

Janet Carreras (16:11)
So I think it's

probably multifactorial. I think, you know, there's definitely situations where like a patient has, ⁓ you know, is coming to see me almost as like the last, the final frontier, you know, of the, you know. ⁓

you know, their experience in this whole cancer thing, you know, they've had CT, they've had surgery, they've had this, they've had that. And a lot of times it's kind of exhausted some of their resources. ⁓ And I think in a lot of ways, ⁓ maybe we need to shift the paradigm a little bit of ⁓ convincing other specialists that maybe we shouldn't be always the last stop in cancer.

Guannan Wang (16:40)
Mm-hmm.

Mm-hmm.

Janet Carreras (16:56)
you know, like the oncologist didn't come last, you know, they should come first so that you're kind of pre-planning, you know, what matters most and, you know, are we saving tissues that we can make, vaccines and frozen tissue as you know, for patients with osteosarcoma so that we can sequence them and, you know, a lot of this is so new that, ⁓

Guannan Wang (16:59)
Mmm.

Exactly.

Mm-hmm.

Janet Carreras (17:22)
those discussions just haven't happened yet. ⁓ And so it's really gonna be a different kind of journey, I think in the future, hopefully, when a patient has cancer ⁓ of when we start to get the oncologist involved. But ⁓ yeah, cost is a hurdle. sometimes owners get overwhelmed. ⁓

You know, my brain as that chemistry major, there's nothing I like more than a pathway. You know what I mean? I'm like, oh, it goes to this, goes to this, goes to this, and the cell divides, right? It makes perfect sense. But they're emotional and they don't know what the right thing to do is. And...

Guannan Wang (17:54)
Mm-hmm. Yeah.

Janet Carreras (18:07)
They have preconceived notions about, just want my pet to be happy and that can't possibly happen if you give them targeted therapy or chemotherapy. So you have to kind of convince them a little bit that this is worth it, you know? ⁓ And I think a lot of...

folks don't know that there are new and exciting treatments that can be so effective, just give it a chance. Nothing's perfect. Nothing works all the time. But ⁓ you really have to educate them and ⁓ take it slow. Help them understand.

Guannan Wang (18:50)
a lot of good points there. So I'd like to comment on the few.

Janet Carreras (18:56)
Mm-hmm.

Guannan Wang (18:57)
So you mentioned that oncology, oncologists oftentimes are the last resolve because the cancer was diagnosed at the GP front, right? And then, they already tried a lot of things by the time they got to you. There's another issue is that the limitation, so there are only so many oncologists in certain state, right? So that's also another big hurdle. sometimes it's a,

Janet Carreras (19:10)
You know?

Thanks.

Guannan Wang (19:27)
hard to get in, get an appointment with oncologist. But by the time they finally see an oncologist, they are already not so financially flexible to try all things that might work better from the get-go. So that's definitely, ⁓ think even awareness, bring awareness, so that's a big factor. another thing is that I think among the oncologists,

There's also, so we also see a paradigm change, ⁓ shift here as well. At the beginning, so most exhaust standard care therapy ⁓ before they try anything new, anything genomic guided, right? So sometimes we, and even our service, we see a lot of cases that come to us that failed pretty much everything. ⁓

Janet Carreras (20:25)
you.

Guannan Wang (20:27)
care, anything you can find in the publications. like not two, three lines, five, six lines of therapy already failed. So this is definitely was pursued as a Hail Mary. Sometimes it works, it actually works, which is amazing, but sometimes it doesn't. So at that point, you would ask the question that it's hard to differentiate, know, there's disease everywhere, spread everywhere, right?

Is it still possible to treat at that point for the patient? And even some of the immunotherapies. So this dog, from the genomic perspective, is a perfect candidate for immune checkpoint inhibitors. However, if the dog is so sick,

Janet Carreras (21:13)
Mm-hmm.

Guannan Wang (21:20)
is the immune system still fit, right, to have the energy and the juice to fight that good fight, even though the tumor is very much, you know, high tumor mutation burden, MRD high, but because it's already so weak, right, the immune system, because of the overwhelming cancer, so that's why,

Janet Carreras (21:23)
Excuse me.

great.

Guannan Wang (21:44)
I encourage all of our doctors to try not use this as a last resolve and also not use oncologist as a last resolve. Maybe test early so that I don't want to say replace standard care therapy that may or may not work, but at least have more options to consider upfront so that you have more options to play with.

Janet Carreras (21:58)
Mm-hmm.

Guannan Wang (22:14)
may generate better results.

Janet Carreras (22:17)
Right, and I think right to your point,

the more we...

experiment, especially with things that won't have great responses to standard of care chemotherapy, ⁓ the more we're going to learn, ⁓ you know, like this works really well, like, we know, toceranib works really well for metastatic anal sac adenocarcinomas, we've been doing that for a long time. ⁓ And ⁓ as as we gain experience, and we bulk up the database, right, even

Guannan Wang (22:28)
Mm-hmm.

Exactly.

Janet Carreras (22:51)
maybe some patients

that can't afford DNA, like I keep calling it DNA, so wrong, genomic testing, ⁓ that maybe we can borrow from what we know from other patients and say, I know you can't afford this test, but maybe we could try this drug, which I sneakily do sometimes.

Guannan Wang (22:55)
Mm-hmm. Yeah. Yeah.

same.

Exactly. mean,

I mean, you know, what we always say that right is that every tumor is different. But for some two for some cancers, you know, the very distinct subtypes that, you know, consists a large proportion of all patients. in those ⁓

Janet Carreras (23:22)
Mm-hmm, yes.

Guannan Wang (23:38)
cancer types, it's reasonable because like for example, standard care therapy, it's 50 % success or failure, it's like a flip of a coin, right? But then with target therapy, you know, kind of like add more parameters so that, you know, you kind of boost the success rate a little bit, right? So, but we know for

Janet Carreras (23:53)
you

Thanks

Guannan Wang (24:07)
for some cancer types recently like in one week I reported ⁓ four lung carcinoma

Janet Carreras (24:16)
Mm-hmm.

Guannan Wang (24:17)
all different. Like we all know, it's so amazing and we all know that, it's lung carcinoma, especially lung adenocarcinoma is frequently found driven by mutations, the one hotspot mutations, in ERBB2, right? But then in this one week, so like four lung carcinoma, all different. Some have this ERBB2 mutation, some don't, some are featured with like a high ⁓ tumor mutation burden.

Janet Carreras (24:19)
Wow.

Guannan Wang (24:46)
Another is high HRD, homologous recombination defect. And the next week, and I saw similar things in hepatocelular carcinoma, three, all different. sometimes you see ⁓ consecutively a few, and they are all different.

Janet Carreras (24:51)
Mm-hmm.

Mm-hmm.

Guannan Wang (25:16)
long

term there is definitely a significant portion of, for example, certain hemangiocirculoma that have PIK3CA and TP53 mutation, right? But like day to day, the patient is very, very different.

Janet Carreras (25:28)
Mm-hmm.

Guannan Wang (25:32)
the recommendation of course is also different, I sometimes think that like if we generalize, that's pretty much what we do with chemotherapy, right? But sometimes I think with the more ⁓ precision or individualized, so like you just don't know what this tumor is driven by.

Janet Carreras (25:43)
Thanks.

Guannan Wang (25:56)
So testing of course is the best case scenario, but I do understand that a lot of times it's just not an option. And then in those cases, we do have to make educated guesses. And we do that. We provide that information to our doctors all the time. I cannot guarantee that this is what is driving the dog's tumor.

Janet Carreras (26:15)
Yeah.

It's it's well and it comes to you.

Right.

Guannan Wang (26:26)
cohort this is what we see I think you know just it's better than going in blind yeah exactly

Janet Carreras (26:33)
Right. Yeah, right. Yeah.

Guannan Wang (26:36)
So are you more leaning towards exhausting standard of care therapy before you layer in genomic guided therapy or do you do combined or do you sometimes even prioritize genomic guided therapy?

Janet Carreras (26:56)
I think lung carcinoma is probably like boom, Right there, hepatocellular carcinoma, right? Those are definitely non-responders to conventional chemotherapy in my opinion. Those are absolutely (I would prefer genomic-guided therapy), So much effort is getting put in to hemangiocerecoma.

Guannan Wang (26:59)
Mm-hmm. Mm-hmm.

Mm-hmm. Mm-hmm.

Janet Carreras (27:14)
⁓ I keep trying

to get the osteosarcomas before everything is decalcified, right? I like I know in my heart that that is like such a important piece to that puzzle. ⁓ I've probably sent you a bajillion melanomas, melanoma, melanoma, melanoma, melanoma, like, like, yeah.

Guannan Wang (27:20)
Yeah, yeah, yeah, yeah.

Exactly. A lot of melanoma from you. Yeah.

Janet Carreras (27:39)
So,

and I see the heterogeneity that you're talking about. I feel like I've never gotten two melanomas that were the same. And I just don't think we can guess, you know, with those. you know, it's a type of cancer that is just off the Richter scale internally. Yeah. So there's no question in my mind that every single one of those patients should be doing.

Guannan Wang (27:58)
Very, very heterogeneous. Yeah, yeah, yeah.

Janet Carreras (28:07)
Genomic testing, you know, there's just but more and more, you know, like I don't see that many aggressive dog mammary carcinomas. But that would be my first having seen like I did kind of empirically pick on my patient and the one who I was just telling you about who's doing fantastically well. Now I'm like, oh, I don't even want to go to standard of care chemo anymore. I'm going to go straight to genomic.

Guannan Wang (28:08)
Mm-hmm. Mm-hmm. Yeah.

Mm-hmm.

Mm-hmm.

Mm-hmm.

Mmm,

for mammary carcinoma. Okay, okay.

Janet Carreras (28:37)
I think it's... Yeah, I would. I can't wait. I have so many

cats Guannan that I want to send you.

and they're, you they have

Guannan Wang (28:46)
you

Janet Carreras (28:47)
so much mammary carcinoma. So I don't really feel like conventional chemo is that beneficial to them. So if I can, you know, it's, think it's about teaching them. And I think a lot of people respond to when you, when you give them examples from their own life, you know, like.

Guannan Wang (28:49)
Mm-hmm.

Mm.

Mm-hmm. Mm-hmm.

Yeah, exactly. Yeah. Mm-hmm.

Janet Carreras (29:07)
HER2 positive breast cancer. People have heard of that, you know, so they can really, yeah, I have heard of that, you know, and you

can kind of hold their hand and walk through. Not everybody has HER2 to positive breast cancer, but it's definitely a thing and you want to know if you do because that's really important in terms of treatment. They kind of, clicks,

Guannan Wang (29:27)
Yeah, that's so true. it sounds like this is a cancer type dependent, whether you will bypass a standard care therapy at all, or you still stick to standard care therapy, and then you go to...

genomic testing and then genomics-guided treatment. So that's sort.

Janet Carreras (29:50)
I yeah, I I think I

try to get them on the bandwagon as early as I can. ⁓ Yeah.

Guannan Wang (29:56)
Right, right, right, right. I think that's the right mindset, you know,

which may make a huge difference in terms of survival, overall survival, overall outcome. Yeah, yeah, yeah.

Janet Carreras (30:06)
Mm-hmm. Yeah. Yeah. I would agree. And it's hard

for us, too. We're really kind of cheapskates. You know what I mean? I hate to say that.

Guannan Wang (30:16)
You

Janet Carreras (30:17)
it's expensive for a lot of people and, but it's so worth it. You know what I mean? That's the whole thing is that it is so worth it to be able to have, treating your malignancy, not what we think of the malignancy in general,

Guannan Wang (30:19)
Yeah.

one size fits

all.

Janet Carreras (30:35)
I just I've definitely

experienced it. and I think ⁓ it starts with that first case was this dog who had.

⁓ a renal tumor they think this is kidney, right? But of course we knew it was kidney because they had removed the kidney and it was really poorly differentiated sarcoma they thought, right? And they weren't even sure. And ⁓ I started that dog on doxorubicin,

Guannan Wang (30:51)
Mm-hmm.

Janet Carreras (31:02)
This is the funniest story. He swallowed a ball and it was a smiley face ball and they tried to scope it out and they kept hitting it and the smiley face kept mocking them. They couldn't get it out. They had to go to surgery and when they took him to surgery they saw a metastatic lesion.

Guannan Wang (31:18)
and then

Janet Carreras (31:21)
So we DNA sequenced that little tumor it was not big, and they didn't even know it was metastatic lesion, honestly, but we ended up DNA sequencing that, and it told us that we should be using carboplatin and olaparib So that actually happened pretty early in his cancer journey. He had metastasis, and then he...

Guannan Wang (31:24)
Mm-hmm.

Mm-hmm.

Mm-hmm.

Mm-hmm. Okay. Yeah.

Janet Carreras (31:42)
He went for like a year and a half on carboplatin and olaparib ⁓ just I think beyond what we would have ever imagined with this dog's outcome. Yeah. he did great, just amazing. So that's when you really start to say, this is really important. ⁓ I never would have come up with that on my own and worked perfectly for him.

Guannan Wang (31:51)
Mm-hmm for a metastatic. Mm-hmm.

Janet Carreras (32:10)
you it's amazing. there, when you kind of have those like successes, then you start to say, wow, I really need to be doing this more often. I really need to, like you said, introduce this frontline. And it's new, so new to the general population of veterinarians

Guannan Wang (32:20)
Mmm.

Thank

Janet Carreras (32:32)
and it shouldn't be, we've been using targeted therapy for a long time and they use targeted therapy every day, right?

Guannan Wang (32:38)
target therapy but not in a targeted manner. This drug is designed as a target therapy targeting certain targets, but we kind of use it as a generic for everybody to see whether it will hit the target or not. This may work for some drugs because they are like, for example, dirty TKIs, tyrosine kinase inhibitors, and they have so many targets

Janet Carreras (32:50)
Right, right. makes sense.

Mm-hmm.

Yeah.

Guannan Wang (33:05)
it's just by random chance a lot of dogs may have one mutation or another in one of the targets that you might hit sometime you see this broader effect you use it without genomic guidance but for other drugs which has a very specific mechanism of action

Janet Carreras (33:18)
Mm-hmm.

Guannan Wang (33:29)
like olaparib is a ⁓ typical one that I often caution doctors to not use it for everybody without genomic guidance because it has very specific mechanism. It only would be effective if the tumor has a defect or mutations in double stranded DNA repair genes such as BRCA1, BRCA2, ATM. ⁓

CHEK1 you have to have a defective double strand DNA repair pathway and then the PARP inhibitor which target the single strand DNA repair pathways it's like a double hit right so you already have a defective double strand DNA repair now we also block your single strand DNA repair so now you have

no way to repair your DNA whatsoever. That's when the tumor is most vulnerable. That's when PARP inhibitor actually can be effective. But if the tumor has a perfectly functional, non-mutated... ⁓

Janet Carreras (34:34)
Mm-hmm.

Guannan Wang (34:44)
double strand DNA repair pathway, then you inhibit the single strand pathway. It won't do anything because the other arm is perfectly functional. some of the drugs are like that. So I want to be very cautious not all targeted drugs can be used in a generic way. Yeah, they actually have to have a target. Yeah.

Janet Carreras (34:51)
bright.

Mm-hmm.

Right, right, yeah, right. ⁓

Yes.

Guannan Wang (35:12)
Yeah. Yeah.

Janet Carreras (35:12)
Well, it's exciting to learn about these new drugs too. It's fun for us to get experience in things,

Guannan Wang (35:20)
Yeah, yeah, yeah, yeah,

still know too little Fortunately, you know, a lot of these drugs we are talking about, begin to use our...

FDA approved drugs for human cancers for many years, right? And most of them have a beagle data like safety, toxicity, PKPD, in healthy beagles. Not ideal, but already better than what we're right now experiencing for cats, right? There's just no, you know, no...

Janet Carreras (35:51)
I'm good now.

Guannan Wang (35:54)
PKPD data whatsoever. if I have to like prioritize, one.

we need to have the right target to use the right drug. But that's clearly not all. Even you have everything perfect, this patient has this mutation which would be perfect for this drug. Sometimes it still doesn't work because there are nuances like toxicity

So this dog just is not tolerating this drug at the standard dose that we are treating with everybody else. So then in those cases, think once we kind of have the main frame more established, use the drug in a more...

targeted within the right patient And then I think there are also nuances that we need to figure out like dosing, So does this dog need this high dose in order for it to be effective? Not necessarily. So there are those nuances that we have to play with, But that's why I always say that we are only beginning to scratching the surface.

but we were already seeing a lot ⁓ of promising stories

I think every doctor that start to use or have been sticking with us to use genomic testing have all have their n of one or n of few success stories. Otherwise, if you don't have one success story, then probably you would abandon me a long time ago.

Janet Carreras (37:20)
Thanks.

I definitely

Guannan Wang (37:47)
Yeah, yeah, Yeah

Janet Carreras (37:48)
I definitely have some really good success stories. I do. like the education to the owner, like you're saying, like it doesn't work every time. Nothing beats cancer every time, but it's, it certainly increases our chances, you know, so, yeah.

Guannan Wang (38:02)
increases our chances. Yeah,

and if we do this collectively in a more, scientifically sound manner,

definitely we'll see more and more of these ⁓ stories and hopefully it will become a trend, will eventually ⁓ change practice, So you had success stories of just using single agent. I remember it's a palbociclib right? Yeah.

Janet Carreras (38:13)
Yes.

Guannan Wang (38:28)
and it's amazing in the metastatic melanoma. But a lot of our doctors, they're not quite comfortable to use single agent, okay, we have to combine it with something, which I think is very reasonable to do. At very beginning, I was like, no, this dog has this perfect target, and this drug should really help. Why?

muddy the water, Otherwise we cannot see what works, what not. But that's also kind of a mindset change for me as well. one, this is

like double insurance, So, okay, so if we do both and if the dog is tolerating both well, then, maybe we can maximize the efficacy,

If we only do target therapy, there is no guarantee that it would work. Sometimes it did, but sometimes ⁓ there's no guarantee. adding in or in combination might work better. That's how human precision medicine, there is also a change. So at first, a lot of these target drugs were approved

the in combination with the standard of care chemotherapy.

But later on, so you see more and more genomic guided treatments are approved. one, more front line and the two more stand alone. So I think, we will get there. We just need to, you know, first the transition from that combination period to, maybe later on stand alone if we see the benefit.

Yeah, true test of success.

Janet Carreras (40:23)
Yeah. And I mean, I

have seen single agents do pretty amazing things. I've also, I was one of those people that you were like, stop saying you're going to use too.

Guannan Wang (40:26)
Mm-hmm.

Mm-hmm.

you got

me really nervous at the beginning. But then I realized that you're not alone. Many do.

Janet Carreras (40:43)
I was like, but why would

we use one if we could do two? yes, I see where you're coming from and maybe it depends on the tumor type and, also the...

tolerance, right, of things, right? Like we know, like going back to toceranib right, as soon as toceranib was available, we were like, let's put it with Vimblastine, let's put it with CCNU, let's put it with Carboplatin, right? Let's see how this all goes together. And, you know, and yet it's not the first thing that I do is always put those two together, right? Because it does have more toxicity. So I think

Guannan Wang (40:58)
Like your own. Yeah, right. Exactly. Exactly.

Mm-hmm.

Janet Carreras (41:27)
you know, it's going to be not the same thing for every tumor type, not the same thing for every drug I remember you once we had a melanoma patient, ⁓ loved this dog so much. had wonderful parents and he was on trametinib and didn't really respond. And then when we added in the sirolimus it was like, know, really dynamic.

Guannan Wang (41:34)
Mm-hmm.

Janet Carreras (41:54)
change in that dog's melanoma. And it was a very aggressive metastatic melanoma I should send you those pictures, Guannan and they're pretty impressive. So, yeah.

Guannan Wang (42:05)
Please do. I love

those stars. Those stars keep us going. We work for it. Yeah.

Janet Carreras (42:10)
Yeah, yeah. So it

was very aggressive. And again, I should have been way earlier in the process. I probably should have had her on targeted therapy. ⁓ But ⁓ it is very impressive to see the pictures because I really thought we were euthanizing her the day that she came in. And I said, let's add in the sirolimus at your advice. And it was amazing. yeah. ⁓

Guannan Wang (42:20)
you

So happy

Yeah of course you guys are the frontliners so you you kind of deal with the worst ⁓

Janet Carreras (42:40)
Yeah.

Guannan Wang (42:50)
stories, but you also have the opportunity to enjoy, these once in a while, you know, right, miracle cases. Yeah. And yeah. And I get to hear more and more of these stories, which are really, you know, keep me pumped in that day. just makes my day. Let's keep them coming. Yeah.

Janet Carreras (42:54)
Great.

Nice.

I will. ⁓

Guannan Wang (43:14)
Yes, so cancer dependent, whether or not you would bypass standard-of-care therapy, cancer dependent, patient dependent, but right now you are more open minded to layer in genomics testing and the genomic guided therapy earlier on.

Janet Carreras (43:35)
Yes. Yeah, no doubt about it. Every, yeah, yeah.

Guannan Wang (43:35)
Right? Okay, that's the, okay. Okay, okay, okay. Perfect,

perfect. Yeah, I just want to understand how you approach this, your practice, yeah.

Janet Carreras (43:45)
Yeah.

I think I'm mostly,

you know, a lot of times I'm kind of going through like this is standard of care. These are the responses that we see, and this is genomic testing and, this tells us about your pet and what the opportunities might be there. ⁓ and, again, depending on what type of tumor it is, like osteosarcoma is, is one where I'm like, we, have a lot of different options now, right?

Guannan Wang (43:52)
Mm-hmm.

Mm-hmm. Mm-hmm.

Janet Carreras (44:13)
have,

Guannan Wang (44:13)
Yeah,

Janet Carreras (44:13)
so kind of if we're going to go with, let's say, amputation and standard of care chemotherapy, wouldn't we want to be able to at least consider like a maintenance, you know what I mean, of targeted therapy if nothing else, because we know we're not done, like, you know what mean, we're not finished.

Guannan Wang (44:32)
Exactly

for those high metastatic prone cancers. You know almost certain that it will come back. So it's always good to have a maintenance. If it's an effective one, if it's a targeted one, so it might just kill those microscopic cancer cells.

Janet Carreras (44:36)
Yeah. Yeah.

Right.

Guannan Wang (44:55)
I think even one to two years ago I was on the airplane was sitting with this human physician so

We start to like chat about what we do and so I was surprised I thought precision medicine in human oncology is prevalent

it's definitely more prevalent than ⁓ what we experience in veterinary oncology. But it's still not 100%. So if you go to a academic medical center, of course, if you are diagnosed, so first thing would be, okay, get your tumor tested genomically. ⁓

So

we'll see what the targets are, what's the best treatment. And they have so many drugs at their disposal they can choose from, which is amazing. But then a lot of community hospitals. this is still not a common practice. when I asked why, so the human physician was also saying, education, we need a lot of education. ⁓ wow, I didn't realize.

that even on the human side, there's still education. So to your point that not everyone, especially for those who have not dealt with cancer, which hopefully keep it that way. then, even for people who have, this might not be presented to them as a routine.

option if they are in the not medical center region yeah so yeah that's why you know like we do need education not everyone know that okay precision medicine target therapy we want to target what's driving the tumor we want to give ⁓

Janet Carreras (46:34)
great.

Guannan Wang (46:46)
the best drug to target this tumor, not one-size-fits-all chemotherapies which may or may not work. Sometimes they do work, but it's always good to have some options.

Janet Carreras (47:01)
Yes, absolutely. Well, and it makes, I mean,

it's certainly changed my resume. now I get all excited if I have a metastatic lung tumor coming in. I'm like, yay, let's do this. it's, really has opened the floodgates on what we might be able to treat successfully, right?

Guannan Wang (47:24)
Mm-hmm what we can do.

exactly. Yeah

Janet Carreras (47:28)
you know to

have to have another layer of options and not stuck in the mud with like i've got these five chemotherapy drugs and you know let me do some magic so gratifying to be able to really take advantage of a whole new formulary right and

Guannan Wang (47:32)
Mm-hmm. Yeah.

Right.

Yeah,

yeah, yeah, hopefully yeah

Janet Carreras (47:50)
precision target for that a dog or cat.

Guannan Wang (47:54)
Definitely. So hopefully, this is going to be a ⁓ positive feedback, right? So the more genomic data we have, the better idea we have ⁓ to use which drug to treat which cancer, which individual. But then that will also have a positive effect to bring more newer drugs, newer generation drugs. So I think that would be ideal.

Janet Carreras (48:02)
Good night.

Guannan Wang (48:24)
Can you still hear me?

Janet Carreras (48:29)
Sorry, my dad is calling me and I apparently do.

Guannan Wang (48:33)
No problem,

yeah. No problem. So, we'll get to go talk to your dad pretty soon. No problem. First I thought it was me.

Janet Carreras (48:40)
Sorry about that.

I'll

Guannan Wang (48:48)
Okay, so I think we touched a little bit on the toxicity side of these newer novel drugs. So what's your general experience? Most of these are oral, right? So do you find that as a benefit or, you know, like it's kind of out of your control or do you see a good compliances of using the drug and good safety?

Janet Carreras (49:14)
Yeah, so I think again, like a lot of it is educating them the right way to do things, right? Like, this is lapatinib I know in about two minutes you're about to ask me if you can give it with just a little bit of peanut butter and the answer is absolutely not, you know? Like, so I think you just have to be really clear with them up front. Like, this is without.

Guannan Wang (49:21)
Mm-hmm.

you

Janet Carreras (49:38)
This is with food. it's a little bit of a different pattern of side effects that we see with these drugs. ⁓ Obviously, each of them is unique, so you have to kind of know ⁓ what to watch for. But... ⁓

Guannan Wang (49:45)
Yeah. Yeah. Exactly.

Janet Carreras (49:53)
you have to educate yourself and then educate the owner. the thing that I always try to tell them is, generally speaking, this is a marathon. It is not a sprint. I would rather you not give these medications if you're concerned that your pet is having a side effect. We can always restart them. ⁓ So just stop it, you know, if you're worried about anything. But overall, most of them are well tolerated, just like

Guannan Wang (49:56)
Exactly. Yeah.

Yeah. Yeah.

Mm-hmm.

Janet Carreras (50:20)
Most of the time, chemo is well tolerated, not every time, right? But I think if they understand that for most patients, the benefit outweighs the risk, right? Then they are open to the idea that they actually have control too. Like, this isn't something that you give IV every three weeks, you're giving it at home. You can stop it if you have any concerns. yeah.

Guannan Wang (50:23)
Mm-hmm. Mm-hmm.

Mm-hmm. Mm-hmm.

Yeah.

Mm-hmm.

Right, right, right, right. So overall,

you think most of them are safe and well tolerated. Of course, there are exceptions to that, but this is same for chemo. But then the oral administration is more convenient, less toxic than the, well, it's still toxic. You still have to wear gloves, I assume, right? When you give the, yeah, of course, yeah, yeah, yeah, yeah, yeah.

Janet Carreras (50:59)
Right.

of course. Yeah. Yeah. Those things don't break open the capsules

and yes, exactly. Yeah. So yeah, I think for the most part and you you're have always like the one-off, you know, kind of idiosyncratic kind of things, but yeah.

Guannan Wang (51:17)
Mm-hmm. Right. Okay.

Mm-hmm. Yeah.

Yeah, yeah, yeah. And we've seen that. We've actually seen them. like the standard dose that we recommend for every other dog work perfectly fine. it just doesn't work for this particular dog. the dog experienced a side effects, toxicities, right? You have to wait for it to bounce back and then consider dose adjustments. and then

because they have the right target and the drug is also appropriate for their target. And then after dose adjustment and it actually worked really well. some things that were never like really on our radar until you actually have these, like patients that are experiencing side effects, right? Then that's become the question, do you switch drug or do you...

⁓ like.

stick to this drug, but consider dose adjustments. So a ⁓ lot of room to work with. is my feeling. And, we ask ⁓ every one of our doctors to send in cases that have experienced side effects so that we can learn from it. We collect all this data so that we can let other doctors know that, sometimes it's a

Janet Carreras (52:25)
a lot to learn.

Guannan Wang (52:43)
very individualized feature. Maybe this dog with this cancer have this ⁓ reaction. even this anecdotal data, we still want our doctors to be aware so that you can watch for these symptoms and signs. All right. So. ⁓

Last set of questions. So ⁓ you are so supportive and I'm so glad to hear that you start to kind of...

consider this early on and you also saw benefits for hopefully more and more of your patients and that's definitely a good trend that we'd like to see. But what other ⁓ changes or advancements would you like to see in this space?

Janet Carreras (53:23)
Thank you.

⁓ I mean, just a lot of the things that you're mentioning, like we're greedy, right? We want more and more and more, you know, targeted therapies. That would be fabulous. ⁓

Guannan Wang (53:53)
Yes, yeah more drugs, yes.

Janet Carreras (53:55)
And

just to kind of like you're saying, learning from each other databases of these are the common ones for this and just even knowing like you can't trust a melanoma, you really probably can't guess. With those, at least that's how I feel that I can't guess the melanoma, just no way. And ⁓ you know,

Guannan Wang (54:04)
Mm-hmm.

Yeah. Mm-hmm.

Janet Carreras (54:23)
relying on a little bit of grassroots, like I did a little talk on, you know, targeted therapy with ⁓ my local veterinarians and their

Guannan Wang (54:28)
Mm-hmm.

Mm-hmm.

Janet Carreras (54:38)
always sensitive to like, how much did all of this cost? nothing is for everyone and not every client is going to be able to do this, but ⁓ it's a little on them too, you should be telling your clients if at all possible to get insurance early on in the game. Open source for people that wouldn't otherwise be able to do things. ⁓

Guannan Wang (54:43)
Yeah. Yeah.

Yeah.

Yeah, yeah.

Janet Carreras (55:00)
But yeah, mean, just

the data, know, sharing data is so helpful. Yeah.

Guannan Wang (55:04)
Yeah, yeah, yeah, yeah,

definitely. Yeah, that's front and center, right? So ⁓

Janet Carreras (55:12)
you very much.

Guannan Wang (55:14)
obviously publish case studies, but also publish peer-reviewed papers of the aggregated data set. I think those are very much needed for the community. that's how we operate. I like to publish papers. Publish good data. And even negative data is also important.

we were right now collecting data for ⁓ response for immunotherapies, right? because now that we have biomarkers to stratify for patients that respond or don't respond for immunotherapies. And this is a well established in human patients that are treated with immunotherapies, but we have

very little data so that's why we are like very actively collecting this data. this will also help us refine our recommendation as well for example cancers with above certain number of TMB like rarely respond to immunotherapy that maybe we should adjust our cutoff right as well so that's I think

Janet Carreras (56:31)
Thank you.

Guannan Wang (56:33)
think

it's definitely something that's ongoing, very much ongoing. But we are very, very much committed to collecting data, generating good data and publish. Yeah. Yeah. Yeah.

Janet Carreras (56:47)
Mm-hmm. So you need more cases. ⁓

Guannan Wang (56:52)
We all need more cases. I'm not greedy. So, and you guys are so supportive. I think you are one of those who really made me do this seriously. Like without your support and some others, this was a big, big leap for me last year. Yeah, you

Janet Carreras (56:54)
Right?

I can imagine.

Guannan Wang (57:16)
we just have been so gratifying of all the support and the data is just amazing. day in and day out, I see these cases and that can...

Janet Carreras (57:21)
Mm-hmm.

Guannan Wang (57:31)
not only guide therapy, right? And where we see more success of responding, but also kind of like refine diagnosis or like even provide a diagnosis for a undiagnosed ⁓ cancer. just very, very gratifying. I'm still very much a data nerd. And when I see this, you know, like my family, they all hear this story.

⁓ you know this case I see today have this and that and it can actually do what so it's just a very very Okay, okay ⁓

Janet Carreras (58:04)
I'm sending you one this week. Go on. I'm sending you one. The thing will work that way. Yeah. So it's a

dog with, they're not sure if it's a mass kind of at the duodenal, like pancreatic junction there. So we don't know whether it's actually intestinal or pancreatic. So I'm like, and I don't think conventional chemo is going to work. So here we go.

Guannan Wang (58:19)
Okay. Okay. We'll see whether we can find out. Yeah,

we'll see we can find out.

Janet Carreras (58:33)
and you're going to

Guannan Wang (58:35)
Diagnosis is not 100 % but we do see more indication of a certain mutations enriched in certain diagnosis. So I'm sure that the diagnostic utility will only increase over time as we learn more.

Janet Carreras (58:51)
Well, and I figure

even if that part isn't made clear that having some, you know, targeted therapy options for that patient is a good example of one that I'm like, I don't think conventional chemo is going to cut it, you know. ⁓

Guannan Wang (58:57)
Yeah, yeah, yeah, yeah, yeah, yeah, that part we're...

⁓ because

the treatment is actually dependent on, even the standard case is dependent on diagnosis. ⁓ I didn't know that part. Okay. That's cool. Okay.

Janet Carreras (59:13)
Yes, yes. Yeah, so I'm kind of like, you know, let's do this direction.

Maybe diagnostically, but it should help us therapeutically. yeah, so pretty exciting. Good example. Yeah, yeah.

Guannan Wang (59:24)
Okay, All right, perfect. Yeah, I'll definitely keep you posted. Excited. yeah, yeah.

Perfect. Any other questions you have for me or any other thing you want to discuss?

Janet Carreras (59:41)
No, I'm just, I honestly,

Guannan you've been amazing. I'm going to tell everyone that you were once on a cruise ship when I tried to get in touch with you about a patient. So dedicated ⁓ and took my call and I'm like, you're on the ocean. you shouldn't talk So, ⁓ but really just an amazing ⁓ service that you.

Guannan Wang (59:58)
Yeah, I am. We are...

Janet Carreras (1:00:06)
provide for our patients and it's just a pleasure always so nice and easy to work with and answer our questions and we're just really fortunate to have you on our team. So thank you. Yes, yes.

Guannan Wang (1:00:19)
Definitely part of the team. Yeah,

thank you so much. Yeah, it's very, very nice. All right. Thank you so much for your time. I'm sure that we will have so many cases to work together and so much stuff to do together. So I'm really, really looking forward to that.

Janet Carreras (1:00:28)
Thanks

Absolutely, me too. All right, take care. Bye.

Guannan Wang (1:00:48)
yeah okay all right thank you okay

take care bye