Doxycycline for Cancer? The Manhattan Project for Cancer Continues with Michael Lisanti
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I'm excited for our show today because we have a returning guest who I've enjoyed having on the program through many years. When we first started our program in WFLA Orlando, iHeartRadio, and now it's become a national program with quite a lot of diverse listeners. But through the years, we've always liked to check in on our friend who joins us now, who is

quite a figure in the world of cancer research and aging research and how they intertwine together is something we'll explore a little bit. We have with us Dr. Michael Asante. How are you doing, sir?

Good to see you again. Happy to be here. It's great to have you on. And, you know, we were just talking before the show, catching up a little bit. But we would, you know, we'll kind of start as if people are meeting you for the first time. I know some of our listeners and viewers will be familiar with you, but many will not because we have people coming and going, as any show has. So I know that you have been involved. You know, the way we found out about your work was an interesting process.

My co-host for the show, Dr. Wei-Ping Yu, who's a NASA physicist, has a very interesting theory about the magnetic property of atoms and subatomic particles. And I said, well, you know, if you're going to make this total revamping of how we think about magnetism in the human body, how would your theory theoretically treat atoms?

how would you look into treating cancer? And he said, I would use antibiotics. And he mentioned Z-Pak. And I said, Z-Pak? He said, yep, Z-Pak. And he explained what he thought was going on at the energetic charge layer of reality that's in our body with antibiotics and cancer cells. And so I looked it up and I said, has anybody ever thought of this before? And I found your work. You were doing

azithromycin and doxycycline to treat cancer stem cells. And so I was just so fascinated by that because I said, you know, how does physics get me to this direction? You know? And so I started diving in and learning about your work. And thankfully we've been able to correspond together through the years. So I know that you're now in Canada, right? You know, you were in England, I think the last time we talked, right? Yeah, no, we recently moved to Ottawa, Canada to, um,

to be part of a relatively new company called Lunella Biotech, which is located and collaborates also with the University of Ottawa, but also other universities in the States and also within Quebec. Well, wonderful. You're back here in North America because you originally started, you know, you were in New York, right? You said you're a fourth generation Italian American. Yeah. I was born in Brooklyn in New York and, uh,

And I started my interest in science actually came out of my interactions with my grandfather. He was a hairstylist, a woman's hairstylist, but also a pigeon fancier. So he he really had a lot of birds. He had about 2000 pigeons and also homing pigeons. And one day he showed me that the pigeon and this is actually very, very relevant. He showed me that the pigeon had a little tumor on its leg.

And he said, I'm going to show you how to cure cancer. I'm going to take a string and I'm going to tie it around that tumor and I'm going to cut off the blood supply and it's going to fall off. This is before Judah Folkman was talking about anti-angiogenesis. So my grandfather, who was very intuitive, actually showed me at a very young age how you could treat cancer effectively with just a piece of string. Wow.

So, and later on, Judith Folkman showed using inhibitors of angiogenesis that that was also a good way to treat cancer as well as other diseases. So my grandfather, although he wasn't, you know, he didn't go to university, you know, he had a rudimentary education. He still was very intuitive about science. And I learned a lot from him, you know, working together with him with the birds. We also had chickens and

fish and turtles. So I was always surrounded by animals and I wanted to figure out how to help people. And so this continued through the years. And I went to medical school at Cornell University Medical College and graduated from the tri-institutional MD-PhD program, which was Cornell, Rockefeller, and Sloan Kettering. And then you went off to, where was your next stop? You went to Einstein then or...

Then I was recruited to work at MIT as a Whitehead Fellow. So that's a junior faculty position at MIT. And there I worked with Harvey Lodish and David Baltimore and many other of the faculty at MIT. And eventually I moved then to Albert Einstein College of Medicine in 1997. And by 2000, I think I became full professor from MIT.

assistant to full professor in three or four years. I was in the Department of Pharmacology there, which sort of jump-started my interest in drug design. So what inspired you to be involved with drug design? Did you have an early interest in solving cancer, or you just had a general technical interest in that subject? Well, I think it goes back to my dad. So in...

When my dad was 58, this is approximately the year 2000, he was diagnosed with Duke stage 4D colon cancer, which was thought to be incurable. And because I was at Sloan Kettering, I was able to talk with the people there and see what clinical trials were available. And so he was able to join a clinical trial. He was actually incurable.

considered incurable. And so they, they had a clinical trial where they would treat him with a compound that was novel and, and they would, they changed the structure of the way they did the treatment. So they wanted to give the drug first and then do radiation first to shrink the tumor and do the surgery afterwards. And so this was called CPT-11. Now it's

actually campathikin and it's FDA approved so he joined that trial and uh he was uh cancer-free for 20 or 30 years after that uh so he was you know so this trial actually saved his life and uh and also there's another message there because he had to be a cure he had to be cleared for surgery so

part of the clearance was doing a cardiac evaluation. So it turns out he had heart disease. So they treated the heart. So the cancer saved his life from the heart disease. And then the trial saved his life from the cancer. So that really had a huge impact on me personally. You know, I wanted, that told me I want to be at the forefront of cancer research and I want to find new drugs that can treat cancer metastasis because he had the metastasis already when he was diagnosed.

And that's the cancer stem cells, right, that people talk about? At that time, we didn't really know much about cancer stem cells. So I dedicated a lot of my time learning about cancer and also about cancer stem cells. And that's, you know, what we're focused on today and the relationship there with aging because we know that aging is actually the most important risk factor for cancer development. Yeah.

Now, here's the thing that's interesting to me, and maybe you can help me understand this better. You know, according to, I looked it up, Google Scholar says you have 122,000 citations. So you're one of the most- Yes, that's correct. Now, here's the thing that's interesting. How is it, you know, that you're, I'm kind of skipping ahead for your life journey we're working on. It's foundationally understanding here, but-

You were the chair of translational medicine at Salford University, right? And that's in England. Yes. And you've been studying this matter of metabolic approaches to cancer treatment. How do you have, you know, so many citations and yet the metabolic approach to cancer is still considered kind of like not even on the radar of like the general public and their perception of what cancer research is doing? You know, I don't understand that. Can you help me understand that a little bit?

It's like you've better, you know, a lot of people are talking about you in academia, but it's not trickling down into pop science or whatever, you know, no one's knowing about our publications and impact. We are laboratory was ranked number one in England. If you look up at research dot com, we're still ranked number one in England. So that's ahead of, you know, other institutions nationally.

Our lab was ranked head of people at Cambridge and Oxford. So we were very fortunate. But I've jumped around a little bit in my career. We've made a lot of different advances in terms of finding new ideas. So, for example, I started out working in my PhD on zip codes, how different proteins are targeted to different organelles.

And so we discovered a new targeting signal there. And then eventually I worked on caveoli, which are signaling organelles. So they are involved in transmitting signals from the cell surface to the nucleus. And then I got interested in how all of this fits together, you know, from a cancer point of view. So

The thing is that I've made a lot of different discoveries over the years that were initially considered controversial, but then turned out to be absolutely right. And so that led to a lot more citations of our work. And eventually we figured out how the cavioli are linked to cancer, and that led to the metabolic idea. So I've sort of spent my entire career following my nose, letting the science tell me where to go, and always trying

found that there are holes in the literature in terms of, you know, some details are missing or assumptions were made that were wrong. So we took that road, at least traveled by other people. And that leads to more citations when you find something is different than other people thought. But I did all of that because I'm just a curious person.

And I guess the biggest, one of the biggest things we understood was the Warburg effect was wrong. Okay. Otto Warburg won the Nobel Prize actually for understanding mitochondria. But he also proposed another idea that cancer cells only use glycolysis, which produces less ATP. And that doesn't make any sense.

you know, numerically because the cancer cells need more energy. So in 2009, we actually proposed the reverse Warburg effect, which is that the cancer cells, so it turned out the fibroblasts, the connective tissue cells were making nutrients and feeding them to the cancer cells, but the cancer cells were using mitochondria. So everything was backwards. So we overturned about a hundred years of dogma. And that also now has been shown to be correct.

And that's why we're particularly interested in targeting the mitochondria, which make the ATP. And the ATP is sort of the currency of the cell. So if the cancer cells have more ATP, then they can go around inside the body. They can migrate. They can metastasize. So we want to turn off that fuel supply, sort of drain cancer's fuel tank, and then prevent metastasis. And it's even better if you can do that with water.

Is your approach to kill the cancer stem cell or to redeem it, to return it to its normal function so it can behave appropriately around other cells? Because the cancer stem cells, which are metastatic, are so dependent on energy, if you take that energy away, they die. You can actually prevent the metastasis by...

inhibiting their ability to make ATP, which is the universal currency inside the cell. So I guess that's why our work is highly cited, is because we've always taken the road least traveled and taken high risks. And that has given us a lot of precedent in founding new ideas and new fields. And so I'm very... We're very lucky that we were able to

Because we were very well funded by the NIH and by the American Cancer Society and other. And also we worked on many other diseases, including diabetes, heart disease, muscular dystrophy. So I have a kind of broad expertise because I went to medical school and I understand the medical thinking, but I also...

did my PhD, so I also have a scientific background. So I'm sort of like a fusion between the two. That's cool. Yeah. And, you know, we've gotten to know a lot of interesting individuals along the way in our research of this because we've made it our goal on this show to not just be a show that just, you know, blindly...

you know, just, oh, what's this? But we really, we see our mission as an investigation that can help change, you know, the discourse and what's possible, you know, because when we have, when we have reports of, you know, children getting colon cancer, I mean, as you've said,

Cancer is an aging-related disease. Why are children getting colon cancer? Why is this happening? This is an older man's disease. In theory, that's what people think of. And now we have 10-year-olds getting this. Something's not right. And I know that you're trained. I know you have a passion, but you're also trained to not think about the horror of

But there's a lot of horror going around here. And, you know, I'm a younger, I'm 36, so I look at things like, how do we change the world quickly? You know, when we have people getting colon cancer at 10,

There needs to be a big, you know, just like they did with that pandemic. You know, everybody needs to be all hands on deck. Now, they didn't get that right, but that's another story. But in terms of getting people to really get excited about a man, I call it a Manhattan Project for Cancer that uses all the information available in the metabolic approaches to cancer and uses, like you said, if it's an aging-related disease, treatments that are well-

refined for that should also help these other chronic diseases that are aging related, like diabetes, right? In theory. And they're together because we found that the fibroblasts, the connective tissue cells, they make metabolites like lactate, ketone bodies, glutamine, which then are transferred to the cancer cells, and then they use them to make ATP. So the cancer cells are robbing

the normal cells of the food and they're acting like metabolic parasites. And the idea is to cut off that connection between the connective tissue cells and the cancer cells. And other people have shown also, and Arglup included, that these fibroblasts are also senescent. So senescence is another word for aging. Basically, the cells

They halt their ability to proliferate and they make inflammatory mediators, but they also become glycolytics. So they make food to feed the cancer cells. So that also would explain why as we age, we've become more susceptible to cancer because we're more likely to be able to feed the cancer cells with our senescent cells.

So if we can get the senescent cells, then we can prevent both potentially aging and cancer. I don't know if you're familiar with his name, Dr. Ray Peet. He was a biologist. He passed away a couple years ago, but he was on my show several times. Have you heard of his name? Sounds familiar. He had an interesting thought about the relationship, and I wanted to just throw this out there to see if you've seen anything that has any information for this in your work. Using...

He looked into the way in which carbon dioxide kind of works. If your body is highly efficient at utilizing carbon dioxide, it's also less likely to have this excess lactic acid, which seems to be that fermented state that, you know, cancer cells thrive in when you have excess lactic acid. And what I was talking about, so they can use that as a fuel. They can take it up and they can convert it into ATP. Right.

So that's like food for cancer cells, the lactococcus. But if you look at the highest altitude areas, they have the lowest rates of obesity, cancer, and other aging-related diseases. And he talked about the effect that high altitude does, which allows your, it basically increases your metabolism to be more efficient at retaining CO2 in the tissue. Have you heard of this? You have to use also less oxygen.

So that would potentially reduce the ROS, the reactive oxygen species that are produced. So that would be one way essentially to slow the aging process by reducing the amount of oxygen in the air. So that would make sense, actually. Isn't that interesting? And I looked at it, and it's true. If you look at the insurance, you know, insurance people know what they're doing with their actuary tables, right? And they show...

that the lowest rates of obesity and the lowest rates of cancer and other mortality related to those aging diseases are always in the higher altitude areas typically. Yeah, because when mitochondria make ATP, they produce pollution, just like a car. When a car burns fuel, it produces an exhaust. The exhaust in the human body is really the reactive oxygen species.

So there's a sort of a trade-off. In order to make ATP higher levels, you need mitochondria, but they require oxygen. But they don't require excess oxygen. So what you're saying makes sense, because if you have less oxygen, then you'll have less ROS, less pollution, less damage, potentially preventing senescence. Yeah, that's interesting. So...

I think a lot of people may have made a mistake going to Florida for their fountain of youth when it's at sea level. They should have gone to the mountains, yeah. You're right. Have you looked at carbon dioxide? I mean, I know that's kind of – have you looked at how that works with cancer? Does that seem to be – It's interesting, but we haven't. We've focused more on the ATP production. Yeah. Because a little-known fact that is buried in the literature –

is that we all make our body weight in ATP every day. And that is required for us to remain healthy. And you can imagine as we age, the mitochondria lose their ability to make ATP, and so there's a deficit. And that's where the cancer cells come in, because they actually boost their mitochondrial potential, and they make more ATP. So the cancer cells...

have found a way to make themselves more ATP and make themselves more aggressive. So all we want to do is normalize the amount of ATP that cancer cells make so they don't take over the body like a parasite. You know, we recently had another gentleman, a biologist from Tufts University named Michael Levin. Have you heard of him?

That's familiar.

detach from that collective mind, so to speak, of cellular electrical signaling, and they kind of forget that they're part of something greater, and they become kind of like reversing back to a more primitive state, like an amoeba-like existence, where it's just gobbling up stuff and acting as if it would, you know, act if it was a single-cell organism. Is that a fair analysis? You know, the cancer cells have lost that

participation in the homeostasis of the body. They are no longer part of the ecosystem, and so they're independent, like an infection. And also, they secrete a lot of inflammatory mediators, just like a bacteria would create inflammatory reactions like sepsis. So there are a lot of similarities between sepsis and metastasis in terms of the inflammation

Same thing with also senescence and aging. You know, inflammatory mediators accumulate as we age, and so we make more and more of them. And so, again, another metabolic link between cancer, aging, and infectious disease. That's wonderful. So before we get into some of the things that you've been working on at your research for treatments,

What do you think is driving this environmentally, you know, this epic increase in cancer? You know, Nixon declared war on cancer, what, in 1970 or something? And then all of a sudden we're having, I know that it's not as button dry as this, but it just seems like we're not winning that war. You know, and I know there's great breakthroughs, but it seems like, you know, like I said, when children are getting these cancers and millennials are getting these aging related cancers, it seems like we're going the wrong way. What do you think?

Just personally, I know that maybe isn't your primary focus. What do you think is driving this accelerated senescence that's creating cancer and all these other diseases? I guess, you know, a lot of it is related to diet, exercise, environment.

People were very sedentary in the 1950s, and they didn't have... That's overrated that they were all running around. They didn't even do cardio at the gym. In the 1950s, they were very sedentary. They got on a train car, went into the city, did their job, came home, and got the newspaper, had a dinner, and went to... Very sedentary, but they didn't have the rates of cancer. What do you think? Is there anything besides just...

We're a bunch of, I'm not saying you're saying this, but you know, the general thought is we're just a bunch of fat, lazy slobs. That's why diseases are just manifesting. I'm not saying you're saying that, but what is it? We're not hitting the nail on the head. We have to, we're not, there aren't very, very many metabolic treatments available in the clinic. You know, the best example is actually metformin. And that was discovered because of the, the cancer connection with metformin was discovered because of diabetes and

So diabetic patients actually take metformin, and metformin is a kind of metabolic poison, but it's not very potent, so it's a weak poison. So what it does is it tricks your cells into taking up more glucose. And what they found is that metformin actually prevents cancer and also prevents aging. So a lot of people who take metformin who are diabetic are protected against development of cancer.

So they investigated that and it turns out metformin is an inhibitor of mitochondria. And that's why the cells take up more glucose because they need to do more glycolysis. So that suggests that mitochondrial inhibitors will prevent cancer. And there's a huge literature there on metformin and people have proposed it actually as a anti-aging drug, anti-cancer drug.

So, you know, our results with doxycycline are very similar because doxycycline also is an inhibitor of mitochondria. So if we want to prevent, you know, these diseases, we need to think about mitochondrial inhibitors. Initially, when I proposed this, I got a lot of negative feedback because

you know people said what do you want to you know give people cyanide but that's not true i mean doxycycline is a fda approved drug since 1967. it's used for six months at a time you know for people who have acne it's a very safe drug and it inhibits mitochondrial biogenesis and uh and the link there is that mitochondria went into ourselves many many years ago you know billions of years ago

and then they became mitochondria. So the bacteria started out as a kind of symbiotic relationship with our cells, and then they were tamed and became mitochondria. So it's no surprise that antibiotics will actually inhibit mitochondria, but they won't kill you. They'll just lower, you know, turn down the volume on the mitochondria to reduce the amount of ROS and also ATP they produce.

So it's actually a very safe way, like the metformin, and it fits together. And then we have another drug that we tested called beta-quinoline. Beta-quinoline is used for drug-resistant TB, and it specifically inhibits the ability of the cancer cells to make ATP. And that also inhibits metastasis. That's a drug from J&J. It's not very well understood why it's toxic, but the doxy is certainly safer than

But that provides proof of principle that ATP is really an important target. So we need to work together to find new beta-molec inhibitors that target mitochondria to prevent cancer metastasis. How effective has doxycycline and beta-quitin... How effective have they been so far with your research? Preclinical models, and they dramatically inhibit metastasis. I think it was...

something like 65 or 85 percent, we've published those results. And then we also had a clinical trial in Italy where we showed in real human patients in what is called a window trial. So the benefit of a window trial is that, you know, the drug is already FDA approved, so you can go into phase two. And this was in breast cancer. So the patients were diagnosed with

and a biopsy was made at diagnosis. And then it usually takes about a month, three to four weeks before the surgery is done. So then you can actually give any FDA-approved drug in that window when the patients are waiting for surgery. So we gave doxycycline for two weeks, and then we looked at the biopsy. Just a regular course? Just a regular course? 200 milligrams twice a day for two weeks. And this is a...

a window trial that was approved by the EU. It was done in Italy. And what we saw, there was a dramatic reduction in the cancer stem cells after the treatment. So that shows proof of principle that in humans taking doxycycline, you can actually reduce the load

What's going on? Are they doing apoptosis, or are they restoring to normal cellular behavior, or what's going on there? We believe it's apoptosis, so they're dying from not having enough energy because they're addicted to the energy. But we saw that a marker for cancer stem cells was specifically reduced, CD44. So we need more studies like that where we take FDA-approved drugs. How challenging is it? How challenging or expensive, or what has to happen to just...

to have like more of those happening all the time you know like those types of studies well we did that trial in the EU yeah and one of the benefits of doing that in Italy was that the cost of the trial was much less so for example uh you only have to pay for the drug and the insurance so then uh it's actually very inexpensive to do the trial we're talking about like maybe 15

20,000 euro, something like that, because the drug is already FDA approved. So you can just use the standard drug from the pharmacy. You just need to prescribe that for the patients.

And then the rest is the insurance because you're working with human subjects. Pardon my ignorance here, but how come if it did, you know, if it got those great results, how come people didn't want to do that a hundred times more? Just keep saying if it keeps doing the same thing, like how hard is that to repeat? Other groups say, hey, let's repeat what you did there. That's pretty good. You have plenty of citations. People know who you are. Did anybody repeat your work? No.

Window trials we need definitely more of those window trolls, but I just I guess I guess what I'm asking is what what's Why isn't there more repetition of this? Yeah, no, no, I guess you know there is you know in order to do those kinds of trials on a larger scale it's very expensive yeah, so for you know large pharma companies there has to be a profit motive there, you know and

So that probably is related. But, you know, doxycycline is actually quite a good drug. And it would be I would be delighted if it was approved for cancer therapy. The problem also is that a lot of people had a knee jerk response when you mentioned antibiotic because they become very concerned about drug resistance, antibiotic resistance. But I think, you know, that is a concern. But doxycycline has a very good history where there is very little or no

antibiotic resistance. Yeah. And people take it for six months at a time for acne, and then they take a drug holiday and they come right back on the drug. So, you know, people... Six months at a time? Yeah, because, you know, it's that safe. It's been around... It doesn't wipe out your good bacteria like they always worry about and all that? Take a probiotic. Yeah. You know, this is... I'm not making this stuff up. This is...

the standard treatment for acne, for example, or acne rosacea. So it's one of those drugs that's not very toxic that can be well tolerated. And so, you know, I'd love to see this move forward, but it's not approved clinically. People can use it off-label, which is what they, you know, you can have it prescribed by a doctor if they're on...

Yeah, I was just going to say there's a lot of doctors that, you know, I remember you were early on, and I don't want to go into the details too much, with the pandemic recommending doxycycline as a prophylactic, right, for these frontline hair treatment groups. And actually, you know, it really did catch on. A lot of people...

A lot of doctors, especially in America, you know, are still, there's a whole, you know, I know a lot of the guys, Dr. Peter McCullough, Dr. Pierre McCullough, excuse me, Dr. Pierre Corey and Peter McCullough and other folks who have been using doxycycline as a prophylactic and as a treatment for that pandemic issue. So it's shown that it can do some remarkable things. And you were right about that. To Dr. Fauci's original research, you know, he actually showed many years ago

early in his career, they actually had samples from patients who had died during the 1920s from the flu. You know, there was the flu pandemic. And a lot of the soldiers, they still had the patient material from those soldiers. And they went back and they looked at the lungs and they stained them. And they saw that those patients had bacterial infections. So they figured out, you know, there's something called bacterial superinfection. So when you have a virus that

It sort of fertilizes the soil of the lung for bacterial infection. But those patients didn't die necessarily. He proposed that they didn't die from the virus. They actually died from the bacterial infection. So what they should be doing and what he proposed in his paper many years ago is that they should be treating patients with viral infections with antibiotics, which is actually what ultimately happened with COVID as well. And I found a trial online also.

from Toledo, Spain, where they had a group in a care home, and they treated those patients simply with an antihistamine because that reduced the inflammation and risk of spread. And if any of those patients then developed COVID, then they gave them azithromycin. And that was another one of the drugs that we proposed. And there were no deaths, no hospitalizations.

So just using an antihistamine and an antibiotic when it got worse was enough to save everybody in this trial in Toledo, Spain. So you don't need necessarily new drugs for these things. You just need to be resourceful in trying drugs.

Things that make sense. It's published online in PubMed, this paper, describing that cohort. A lot of folks who, Ivermectin got a lot more folk interest than Z-Pak and doxycycline in terms of public consciousness during the pandemic. But I think that doxy and Z-Pak were the dark horses for a lot of people because they would take that

There's a lot of those frontline doctors that were kind of rebelling against the establishment protocol of just sitting there and waiting until you're blue and then go to the doctor for your oxygen. The other thing that worked quite well for me and also is in the literature is carnitine. So there's something called...

cardiac inflammation that occurs with COVID. And this is sort of off the track, but it's important because, you know, that can also lead to tachycardia and death. And my daughter was 15 at the time and she didn't get the COVID vaccine because it wasn't licensed yet. It wasn't legal for her to get it until she was 16. She was like two or three months between

her, you know, becoming 16 and she got COVID. And fortunately, I read online that people had used carnitine, which is an amino acid, which reduces cardiac inflammation. And I was able to give that to her. And initially, you know, her heart rate was 160 beats per minute or higher. And, you know, the NHS was not functioning well at that time.

So there was no real infrastructure that could help her. And so I happened to be also taking carnitine as a supplement. And so I gave her the carnitine and within a matter of hours, her heart rate went from 160 to 130 to 120 to normal. So also was very important. That's not an FDA approved drug. That's a supplement that was also reported online to be beneficial for

for cardiac inflammation, but again, something that is not well transmitted to the public. So you have to be both a scientist and also a doctor to, to, to data mine the internet, to find these interesting possible solutions, especially during crisis. Yeah. Uh, I, I, um,

Yeah, that, you know, Paul Merrick is another doctor who did a study on showing, he used fen, I think it was something related, not fenbendazole, but another one like it. And then ivermectin. Ivermectin. Now, those were more popular than doctors. I don't know why. Maybe you have an idea. But why is it because that you had mentioned that cancer functions like a parasitic-like

entity on the body and therefore, I don't know. Yeah, it's very much like a bacterial infection. And, you know, that's something that's been floated around. But, you know, we have really good hard evidence that it's the mitochondria in the cancer cells that are really dysfunctional target ultimately. And they're more energetic, making more ATP so they can take over the body. They can migrate and metastasize.

and you originally were you were studying azithromycin zpac why did you kind of hone in more on the doxycycline is it because of the heart considerations that people have about zpac well they're they're both similar in the sense that they are inhibitors of mitochondrial biogenesis so in the mitochondria they have their own ribosomes to make their own proteins and the doxycycline is an inhibitor of the small mito ribosome and the azithromycin

is an inhibitor of the large mito-ribosome. So they actually hit the same target because the large and the small mitochondrial ribosomes are connected to each other, and they're required to make the most important mitochondrial proteins that are encoded by the mitochondrial DNA. And so we could actually show in a paper that's published that if we give a little bit of doxy and a little bit of azithromycin in aging studies in worms, there's something called C. elegans, which is used for

aging studies because they have a very short lifespan, one to two weeks. We could double their lifespan just by reducing the mitochondrial power using doxy and azithro as a combination. And so that also sort of goes together with the idea that cancer is an aging-associated disease. And using those drugs, the same drugs we showed kill cancer cells, can also extend lifespan

We can't do that same experiment with humans because, you know, that would be 80 or 100 years, you know, to do that kind of trial. But we can do it in worms, which have a shorter lifespan. And we can see that reducing mitochondrial power will also extend lifespan significantly.

Wow. Now, you know, speaking of increasing aging related to other animals, that reminds me of another thing Dr. Ray Peet taught me. He pointed out the naked mole rats. They are very similar to regular rodents, but regular rodents have a few years to live, whereas these naked mole rats can live to be 30, 40 years old. And what they do differently is they block off oxygen. Yeah, it may be that way.

They use metabolism also, like you were saying, going to the mountains. Instead, they go underground. So is the idea in general to prevent and to create, is the theory to...

to increase metabolism overall from the body or is it to target the metabolism selectively of these dysfunctional cancer cells or both? What's the big picture here? That's why people say exercise is good for you because it essentially increases the metabolism of the body, the muscles, and then the cancer cells, it's sort of a balance. So then if you increase the ability of the body to make more ATP and become more oxidative,

then it leaves less free food for the cancer cells. The other way, which is easier, you know, it takes a lot of hard work and dedication to do the exercise. The other way is to essentially attack the mitochondria in the cancer cells. But both would work, essentially pumping up ATP production in the normal cells or inhibiting the mitochondria in the cancer cells. They would

be predicted to have the same net effect, which is to nullify the cancer cells. I mentioned this briefly before, but a student of Ray Peet, Georgie Dinkoff, who's a friend of mine, I recently had him on my show. He did a study in rat models using the J-E-K-1 human mantle cell lymphoma, which is highly lethal cancer, and he used

Vitamin B1, which is thiamine. Vitamin B3, which is niacinamide. Vitamin B7, biotin, aspirin. And he gave them a single daily oral dose. And these B vitamins, the idea...

is that the thiamine supports mitochondrial energy production, the niacinamide restores the NAD+ to NADH ratios, which is critical for oxidative phosphorylation, and biotin enhances the citric acid cycle. And then the aspirin acts as an anti-inflammatory and enhances the mitochondrial ATP synthesis

by inhibiting pro-inflammatory enzymes. And within days of treatment, the rats had complete tumor regression and continued to live on well past the expectation of what that would be. The way I would explain that is that it was boosting the mitochondrial metabolism in the normal cells. So then they could more effectively compete with the cancer cells because...

Cancer cells are foraging for free nutrients. So if your normal cells are not as well equipped with the mitochondria, then they can't compete for the nutrients with the cancer cells. That's the way I would interpret it. Yeah. Obviously, it requires more experiments to figure out if that's the case. Right.

I mean, think about this for a moment. You're talking about doxycycline, one of the cheapest, most widely used drugs, a generic drug used all over the world. And here I'm talking about vitamin B1, B3, B7, and aspirin. These are the cheapest things you can get worldwide for anything, you know. And these things could be making such a big impact on cancer. I mean, vitamin B is another one.

Yeah. Now, this drug was also used by the Care Oncology Clinic in London. Which drug? Doxycycline? Doxy. It was one of their four or five different drugs that they would rotate for patients with advanced cancer. And all of the drugs that they used were actually also mitochondrial inhibitors in addition to the doxy. But doxy was one of them, and that was really based on our research. Wow. Have you looked at aspirin at all and how that works?

I haven't, but I know from the literature that it actually also has anti-cancer properties. Yeah. And that also is work...

that was done in England for preventative assessment of aspirin as well. I think it was in colon cancer. When you think about the cost of these chemotherapies and everything like that, you can imagine there's a lot of industry pushback from the idea of letting doxycycline and aspirin...

become widely known as potential effective therapies for this disease, you know. Well, the key is that also they're FDA approved, you know, so you can get them if you need them. But we did make a more efficient analog of doxycycline, and that was largely because we wanted to see if we could make it more potent and increase the selectivity. And that was called doxymyr.

which we published and patented. And that one also is very interesting because adding the meristate blocks its ability to act as an antibiotic. So that takes away the possibility of antibiotic resistance. So that may make it more palatable to the medical and pharma community because it's no longer an antibiotic. Now it's only an inhibitor of mitochondrial biogenesis that targets cancer stem cells with five times more selectivity.

Yeah. So, you know, when you look at, you know, do you have a, you know, knowing what you know, do you have other environmental changes that you have thought to be important if you want to prevent or, you know, just not get to the point where you need to be

in the quandary of the traditional medical centers saying, okay, it's time to chop, burn, and poison. And then you see people like Michael Asante and these folks out there in the research world, and they seem so far away from your reality of being inundated with all these scary treatments that are just going to blast your body into... I wrote an article, and it was published in The Conversation, and I discussed this, just exactly what you said about chopping,

burn and poison. I talked about, you know, that's the conventional cancer therapy. I wrote an article for the conversation about that. And the fact that we identified the cancer stem cells, we identified them, you know, I think the best proof of principle for us was we used an existing probe that turns red when it binds to ATP. And so we were able to take the total population of cancer cells and

and then add this little probe, and then purify the cells that had the most ATP and the least ATP. And we showed that the cells that had the most ATP, the cancer cells, they were the most metastatic. And they were also the ones that we could target with drugs that inhibit mitochondrial function. And we published that, I think it was 2022. And recently in another paper,

We provided additional evidence because mitochondrial DNA is required for mitochondrial function. So we also used another probe that only binds to mitochondrial DNA, purified the cells that had the most mitochondrial DNA, and those were the ones that were the most aggressive, drug-resistant. And we could also show that a drug that inhibits mitochondrial DNA replication would prevent metastasis. So we have three independent studies.

types of experiments that show with different drugs that metastasis is strictly dependent on ATP production. So we could walk up and down that signaling pathway, that metabolic pathway, you know, connecting mitochondrial biogenesis to ATP production to mitochondrial DNA replication. All of those are required for proper mitochondrial function in the cancer stem cells. And in all cases, we could show

that that would actually inhibit metastasis. And so that shows that that pathway is something that is, you know, targetable and also functionally inhibiting metastasis. So I think we and others need to do more research in that area, but that's a very promising place to be. Wow. What would you say needs to happen regulatory-wise in America to make this easier to get to the public? Like I said...

If you're an ordinary person listening or watching this show and you know someone who has cancer, you sound promising, but of course you're still in the research world. Your vision, right? People don't want to have cut, burn, poison. Every time you see that the

especially the longer they do the chemo and everything like that, it just blows out the immune system and the body just really never fully recovers a lot of times unless there's some extraordinary circumstances. Yes, you know, it would be useful to have something like the care oncology clinic also in, you know, the U.S. and Canada. I think they're working on that. I think that's happening. To do what? What are they working on? This care oncology clinic where you can get –

that type of protocol, you know, that uses, repurposes FDA approved drugs. They're doing that right now? Wow. Yeah, I think it's still going. You'd have to double check, but I understand that they're... Are they doing your things or different? They're doing doxycycline and things like that? They're using doxycycline, yes, but we're not involved with them directly. They just read the literature and then, you know, adapt that. But they are focused on

using and repurposing FDA approved drugs, but they're working together with the physician. So they're not against the physician, they're working together with the doctor who made the diagnosis. So because at a certain point, and it's unfortunate, a lot of patients get to that point where there are no other things to try.

And so then the doctor, their physician runs out of options. But there is still the care oncology clinic. It would be nicer if they actually contacted them sooner. But I think there is this opportunity to work with organizations to also make this type of protocol available where we also use repurposed drugs regularly.

and i'd be happy to be involved in that or talk to people about that you know give them my uh benefit of experience with

making referrals, for example, to the care oncology clinic. I've made a lot of referrals to them informally. People will come to me and I'll connect them. Where are they at? They're located somewhere? All over the world. Oh, okay. But they were located in London. I think they were recently bought by another organization. But they're in America too? I think they are. They have little clinics or they just coordinate with local doctors? I haven't gone. I've only spoken with them on the phone.

or by email, but I only went once to visit them in England, in London. They were in Harley Street, and they had a small office, but they would work together with the doctor, and they would prescribe the medicine, and it was set up like a trial, so that it took all comers, and they did publish a few papers here and there showing that actually that it extended lifespan, especially in lethal cancers like glioblastoma.

I wonder what it would take to get that, you know, things like these vitamins and, you know, you've talked about vitamin D being so important and people are, you said they're chronically deficient with vitamin D and that's important, right? To get that not. He also has a lot of importance for the mood as well. You know, a lot of people,

are vitamin D deficient and underlying, you know, they have also an underlying depression. Yeah. There's a big link there. So, you know, that could also be used to prevent depression. I mean, that's also a very big disease, you know, and also a lot of people are vitamin D deficient. So they need to get tested. Yeah. And they need to take the necessary supplements to prevent depression.

you know, cancer and also depression potentially. I wonder how many, I want to ask you like factors that we think of the last hundred years, cancer has gone from relatively rare disease to this huge,

thing, and those who are in the Western societies are very acutely aware of this. In societies that are still indigenous, indigenous diet, you don't see rates of cancer in some of those ones that are still isolated in the Amazon, isolated in the Pacific Islands like Papua New Guinea and Vanuatu. There's all these places where you can still get a window into the

traditional diets of variation. Some are high carb and low fat, some are high fat and high meat and low carb, like the Hadza and the, what's the other tribe? I can't think of it right now, over in Tanzania, that people have studied. They have very low rates of these chronic diseases and senescence-related diseases.

What do you think are the environmental biggest culprits that people need to practically consider? And maybe you haven't looked at it at all, but I'm sure you probably, you've spent your whole life studying aging and cancer cells that you probably could give us some tips that the average Joe might benefit from. Like, is it the high sugar increase? Is it the high omega-6 fatty acids that are in seed oils, these industrial seed oils that have all these horrible inflammatory properties?

chemicals when you heat them especially or fry things in them. Is it blue light exposure? No, really, but I'm fortunate in that my wife is Italian and she likes to cook. And we work together also. You eat plenty of pasta then, right? I am on the Mediterranean diet a day and I'm very fortunate there.

So a lot of olive oil, a lot of natural things. So you don't do a low-carb diet, right, as Italian food? Well, it's mostly the Italian diet, more or less. The Mediterranean diet is not exactly vegetarian, but it doesn't have a lot of meat in it. Maybe we'll eat red meat once a week. So if you look...

A lot of the Italian cuisine is a lot of vegetables, a lot of fresh fruit. So I don't actually, you know, I guess I believe that the Mediterranean diet is quite good for you. But I also take some dietary supplements. I guess that would be another...

discussion. But obviously, I think you can, aging is malleable, cancer is malleable. You can take things like vitamin D to make sure that you don't get deficient. You know, there are a lot of things, a lot of supplements that are now widely available for prevention, for example. Yeah.

I really appreciate your time. It's always great having you on, and I hope that those listening can share this and think about these ideas. It's great to have you back in North America. Maybe we'll, proximity, do more together now that you're closer to the neighborhood. Sounds good. Nice to see you, David. Thank you. Have a good one. ♪♪♪

Bye.