Tom Anchordoquy, PhD, Professor, University of Colorado, Skaggs School of Pharmacy (and Pharmaceutical Sciences), talks about the research being done in the chemotherapy world and how experts are working to orally deliver these treatments to patients in a home setting.
Interview conducted by Ivanhoe Broadcast News in December 2018.
Let’s start with an overview of chemotherapy and what that does to patients, the impact of chemotherapy on patients?
Anchordoquy: Chemotherapy is made up of really toxic molecules. We’re trying to kill the cancer more than we kill the person, so that’s the balance. The side effects of chemotherapy are pretty extreme. People lose their hair, they lose their appetite, they get sick, and sometimes they die as much from the chemotherapy as they do from cancer.
And this is across the board, lots of cancers, people need chemotherapy for?
Anchordoquy: Yeah. Chemotherapy and radiation therapy are the standard ways to treat cancer. I’d be misleading you if I pretended to be an expert in chemotherapy, I’m not.
From the people you’ve worked with and the research you’ve done, the patients you’ve talked to about this, certainly chemotherapy has a physical toll, but mentally it must have a toll as well. And just kind of interrupting your life, trying to live, when you have to keep coming back to the hospital.
Anchordoquy: Yeah. I’ve never been through chemotherapy, but most of us, even someone young like yourself, has probably known someone to go through chemotherapy. It’s a pretty taxing endeavor and obviously life-threatening. So yeah, it’s very disruptive. It’s disruptive on the whole family.
What’s the benefit? If you could take the person out of the hospital setting and have them do this at home, I mean, they’re still going through chemotherapy, but what impact would that have?
Anchordoquy: Well, just the convenience of not having to leave, for one, and that’s a huge inconvenience. I think it’s a little easier to pretend that things are normal when you don’t have to leave the house and go to a special big building where you don’t know anyone. I think there’s a lot of emotional comfort with that. But in addition to that, just the exposure to other people. When you’re sick and you have cancer, you are immune suppressed. So your potential for getting a bug, getting sick, a cold, flu, picking up some other kind of infection, are really high. If you can stay at home and limit how many people come into your space, how many people you’re exposed to, your chances of not getting sick are much better. If you go to the hospital, you could get exposed to other sick people. Getting exposed to those sick people is a real drawback. And the mortality rates of people who have to go to the hospital versus getting treated at home are significantly higher. That’s known.
I know you’re not an expert in chemotherapy, but how is chemotherapy given currently and why isn’t it done orally?
Anchordoquy: Some chemotherapy is given orally, quite a bit of it. But, for the reasons I don’t fully understand, I suspect the doses are too high for oral availability, and some drugs, just whether they’re chemotherapy or not, some drugs just cannot survive the conditions in the stomach. They’re either degraded in the stomach, or even if they’re not degraded in the stomach, oftentimes they just cannot pass out of the gastrointestinal tract. You swallow to get the drug into this tube, and it’s got to go from that tube into your blood. The ability to absorb the drug isn’t good. That depends on the chemical properties of the molecule.
There are some drugs that can be given orally, but those drugs don’t work for all cancers, right? So you need some specific drug. Is that what this is doing, going after the specific drugs that cannot be given orally?
Anchordoquy: Yes. Or a better way to say that is, drugs that are given intravenously, for many reasons. I don’t know all the reasons, but for whatever reason, they’re given intravenously, which means they are typically given in the hospital.
And are these drugs for common cancers?
Anchordoquy: Oh, yeah. Breast cancer for instance.
So it’s just specific drugs. Other drugs can already orally be given?
Anchordoquy: Yeah, there’s oral chemotherapy.
Because there’s lots of different chemo drugs.
Anchordoquy: Right.
Tell me about the thought process behind this research. And where this came from, about attaching these drugs to milk particles?
Anchordoquy: Well, I would love to take credit for all that but that would be disingenuous. The reports of this idea or this phenomenon had been in literature for the last few years. People have been reporting that these little particles from milk can actually get in to the blood. Their concerns were things like, you’re eating cows milk, especially kids consume a lot of cows milk. So the particles in the milk may be affecting the kid. There are several papers saying we should be paying attention to this, this may not be good. We don’t know what this does, nobody has ever considered this before. In addition to that, it’s not just me, it’s the other people here in the lab. Our addition to the story was that we understand how that process works. How it exchanges or how it moves from one tube, how these particles from the milk get out of this tube and into your blood, the digestive tube is what I’m talking about.
What’s the benefit? Some chemotherapy, it gets destroyed in the gut. Tell me a little bit about that, what this role would be for milk.
Anchordoquy: Right. Your stomach is very acidic, right? That’s how molecules get digested. So when you eat a hamburger or salad or whatever, it gets in your stomach, and it gets broken up by the acid, as well as enzymes that chew up all the molecules that compose your food, and break it up into little tiny bits, and then those little bits get absorbed. So if you’re taking a drug, you don’t want the drug to get broken up in little tiny bits, right? You want that drug to remain intact. This particle essentially encloses the drug, encapsulates it in a particle. This particle then goes in and protects the drug. It’s like you’d be surrounded by a shield, essentially. Then this whole particle gets moved from the digestive tract into the blood, and then the particle circulates around your blood.
Why don’t milk particles get destroyed?
Anchordoquy: The quick and easy answer is that they’ve evolved to withstand this. A cow stomach isn’t that much dramatically different than ours, in the sense that it’s acidic and has enzymes and things like that. So exactly why these particles are able to resist that is unclear, but they do.
Do you think it’s because mammals need the milk from their mother and they need those antibodies?
Anchordoquy: Absolutely. I’m sure if we looked in human breast milk, and people have, you’d see particles very similar. Evolution has ensured that these particles are made in such a way that they can resist the acid and resist the enzymes and pass the material to the baby.
How are you attaching chemo drugs and these medicines to the milk?
Anchordoquy: That’s the magic, isn’t it? That’s the technology we’re really working on, how to load these molecules, drug molecules, into this particle. And you don’t want me to go in to that.
I do a little bit. If you have kind of an explanation you would tell someone who doesn’t know what you do. Just that kind of explanation?
Anchordoquy: Yeah. A lot of things are not water-soluble, they’re oil soluble. So if you pick a drug that’s more oil soluble, and then you put it in oil and you dilute out the oil with water, that molecule will not be soluble anymore. It’ll precipitate. But if you give it an environment where it can, instead of precipitating, it will partition into an oil-like environment. This shell around these particles in the milk, have a kind of oil character to them. So the molecule, what we call ‘partitions’, they’re just given a choice between dropping to the bottom of the beaker or moving into this oily environment, and it’ll move into the oily environment. You just have to play with conditions to get that to happen just right.
Where are you in the research right now?
Anchordoquy: That’s where we are. Loading drugs in and characterizing how much is in there.
Are you testing lots of different drugs to put into the milk thing?
Anchordoquy: Right now we’ve we just focused on one drug, but we’re about to start some other ones.
And this is the chemo drug that you’re working with?
Anchordoquy: Yes. But learning how to manipulate these particles and the conditions you can use and still keep them intact. If you start putting these particles in too harsh conditions, you’ll destroy the particle. So there are things to learn about how to manipulate these particles.
What are you seeing as this research is evolving? What are you learning?
Anchordoquy: Well, we’re learning the limits of how we can torture these particles before they fall apart.
But are you also seeing that, yeah, this is possible?
Anchordoquy: Oh, yeah. Other people have loaded drugs into these particles, and we’ve loaded drugs into very similar particles. Particles not from cow milk, but very similar particles that other cells make. They’re not in milk, but they’re in blood for example. So they’re very similar particles in terms of their characteristics and their origin. They just didn’t come from milk. We and others have loaded drugs in those particles, so now it’s just a matter of applying what we knew about those to the particles in milk.
How far out are we? What are we looking at before you can get these specific drugs into patients?
Anchordoquy: Well, this particular drug that we’re focused on, we’re hoping to be doing animal studies in the next month. We’re working with some clinicians; we might be trying this in people in potentially a year, two years. That’d be pretty fast, but that’s possible. We’re at a great institution here, where we have the research labs we’re standing in now. Then if you walk a little bit that way there’s the hospital. So we have people that go back and forth and we’re working with some of those people. If this works, they have patients who are willing to try it. They can potentially get that approved and try it on people.
What kind of impact could this have on patients?
Anchordoquy: Well, it would enable them to stay at home and get their chemotherapy. The other potential is that we can use drugs that don’t work now. One of the drugs we’re trying is a drug that can’t be given to people because it doesn’t get absorbed at all, essentially. It just doesn’t dissolve well, and doesn’t get absorbed. But it’s known in animal studies, you can test these in animals and show that some molecules work very well on cancers in animals. They probably would work well on people; except you can’t do the types of experiments on people that you can do with animals. So some of those drugs, we can load into these particles.
So this drug can’t even be given intravenously? This isn’t an option at all for patients?
Anchordoquy: Correct, right now, yeah. It opens up new drugs. We’re not developing new drugs, but there are compounds or molecules that are known to work very effectively on cancer that just cannot be given to humans, because they’re either not soluble or they’re too toxic. Things of that nature. By putting them in these particles, we can hopefully minimize their toxicity a little bit and make them a little more amenable to human use.
Is it possible that side effects that we all relate with chemotherapy now would be decreased?
Anchordoquy: It’s possible; it would be great if that were happening. I think it’s unlikely that the side effects would be lessened significantly. We still have to get the drug to the cancer, and there’s going to be some collateral damage. Some other cells are going to get the drug, and it’s going to do damage. It’s probably not going to minimize the side effects that you’re used to, but it would minimize the trauma of having to go to the hospital every day for six weeks.
Great. And what’s next? I know you’re starting the animal studies. Take me through the next year or two, what you’re hoping.
Anchordoquy: Well, we’re going to try to load different drugs. Chemotherapeutics, what we’ve been talking about, most of the interviews I’ve done focused on that. But another big one, if you know someone who’s had a systemic infection. A lot of elderly people, from dental work, they’ll get a bacterial infection in their blood. The only way to deal with that is to have intravenous antibiotics. And the reason a lot of antibiotics can’t be taken orally is because you can’t get enough of it into the blood if you take it orally. They have to go the hospital for that, just like we talked about for chemotherapeutic patients. So we could potentially load antibiotics in there and make that process a lot easier, too.
I mean, we’re talking chemotherapy, I didn’t consider people could be using this research for other drugs. So things like insulin, and stuff like that, could this work?
Anchordoquy: Yes. Obviously insulin would be a huge money-maker, and there’s tremendous interest in that. I think that’s not on the top of our list, for reasons that I don’t think I want to bore you with. If you want to be bored, I can do that. But I think, yeah, you could apply this to lots of drugs that you’d be taking intravenously. Obviously insulin is one that many people are familiar with and would have a huge effect, if people could just swallow their insulin instead of having to inject themselves. I don’t think, for technical reasons, that that would be all that easy to do.
Right. The dosing, probably.
Anchordoquy: Well, it’s a harder molecule to work with. And because it binds to the outside of cells, binds to a receptor, we know that these particles, once they get in the blood, are taken up into the interior of cells. So we really need drugs that work on the inside of cells, not on the outside.
I see, okay. To reiterate, these drugs, you’re not just trying to get them to be digestible, you’re now trying drugs that could not be given before?
Anchordoquy: That’s our first drug that we’re trying, is one of those. And the sky’s the limit for that. The problem in our situation is we’re a small lab. We cannot invent new drugs. So we have to use what’s available. A lot of the drugs that are amenable to this, we don’t have access to, because companies tried them, they didn’t work, and so they threw them away. So we can’t buy them and try them, we don’t even know about them. This particular one is well known because it works so well, and they tried for so long to make it amenable to humans but it just didn’t work. As a result, what they did was they put this molecule into another very common drug that is given to humans. But that drug is about 100 to a thousand times less potent than the drug we’re using.
Can we use the name of the drug you’re studying? Does it have a name?
Anchordoquy: The drug that’s given to people is ironotecan, and then it’s the active form of ironotecan is what we’re trying to use now. We just filed a provisional patent yesterday.
Is there anything about this, along this journey, anything that has surprised you?
Anchordoquy: What surprised me is the media attention. I’m standing here in my lab, which normally I don’t really even go into. These people control this place, and appropriately, do not let me in here. So what surprises me is that it is a really cool story, I figured it would be of interest to people. But Jackie and Stephanie did such a good job, and they’ve filmed this patient, and they’ve made such a good story out of it that, I’ve been on almost every channel in Colorado. I’ve been on press releases, I have people contacting me from all over saying, oh, I saw you on this press release or whatever. Then here you are doing a story that’s going to make national media. That’s what surprised me so much. The fact that we have yet to really do anything to affect a single patient, and yet the media attention is so high.
I think that the impact this could have on patients, it’s just so widespread, and everybody knows that chemotherapy looks like, even if they haven’t directly experienced it, the drip, what that does to people.
Anchordoquy: I think you’re right, the potential impact is enormous. But I also think the story is very compelling. The rancher who gives us the milk, I mean, this was a pretty crazy idea when I called this rancher. I called several of them who never called me back. She called me back, and said, wow, this sounds really interesting. So I mean, from rural Colorado right here to the labs and potentially all around the world and helping cancer patients. I think it’s a story that people can understand. Most people understand that when mothers nurse their babies, they’re passing material, not just nutrition, but passing material to the babies that is helpful. These particles are something that I think, until now basically when our study will come out soon, people didn’t recognize that these particles were actually getting into their babies. Or how they were getting in, certainly, until our paper came out.
And that just reminds me of another question I should have asked, so you are working with the local farm. You’re just getting raw milk from them? How are you doing that?
Anchordoquy: Just to put people at ease, the milk you get in the store has very few of these particles, so you’d be hard pressed to get enough of these particles to do anything by just drinking milk from the store, even if you drank a lot of milk. The homogenization process essentially beats up these particles and destroys them. So we have to get raw milk right out of the cow. We email or call Pam and Jeff, Mucca Bella Dairy up in northern Colorado. And Jeff works at a city about an hour from here. Brittany or myself goes, and we call them up, and they say, well, we’ll give you a quart tomorrow or half a gallon, as much as we need. We typically can only really use a quart or so. That gives us so many particles, we can’t use more than that at a time. So we get a quart of milk, he brings in an ice chest, we go with our ice chest, put the quart in our ice chest, and we bring it here. And then Britney and Jamie work magic, and they get the particles out of the milk, and then we start trying to load drugs in it. The equipment behind me is the equipment Britney uses to quantify how much drug is in there. I think it’s not hard to get some drug in, but ideally you’d like to maximize how much drug you can get into these particles, without destroying the particle. And that’s the trick, that’s what we’ve been working on.
Once you get particles out of the milk, because milk probably doesn’t last that long, but once you get the particles out, does it have a short halflife? How quickly do you need to work?
Anchordoquy: That’s a good question. I don’t think we know that for sure. But these particles, we can freeze them. They last a pretty long time, certainly weeks if not months. We envision a process by where we’d load them with drug, either freeze them or dry them, and then you could put them in regular food or just take a dose of them yourself. If we froze them, and you could put them as a topping on ice cream or something, and you could eat that. If we dried them, you could sprinkle them in anything, sprinkle them on a salad, things like that. Another thing to know is that there’s very little lactose left, and you’ve gotten rid of almost all the milk. There are just these little particles. So I don’t think that lactose intolerance would be a limitation. But that’s something we don’t know yet for sure.
Awesome, very well explained. Is there anything that you think we should touch on, anything that I left out?
Anchordoquy: No, other than I’m the person here standing in front of the camera but the people who deserve the credit are sitting over there. They’re the ones who did the work. I just got the idea, and then they do the hard work. It’s easy for me to sit in my office and come up with ideas. That’s easy. And some of these drugs probably could be given orally, but the doses you need, the concentrations of the blood that you need, are so high for certain cancers, that the only way to give them and get those concentrations is intravenously. So that means you got to have a sterile solution, right, and somebody trained has to administer it, and that costs money. Doesn’t necessarily have to be done at the hospital, but somebody has to travel to your house. And it’s got to be packaged sterilely. If you had dry milk particles, anybody could administer them, and you’d swallow them. Make things a lot easier and cheaper.
END OF INTERVIEW
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