#412 ‒ The evolving science of cancer: emerging approaches to prevention and early detection, and the advances reshaping treatment | Siddhartha Mukherjee, M.D., Ph.D.

“of a sudden it says, oh, maybe just like lipitor for cardiovascular disease or hypertension for cardiovascular disease, maybe I have a marker.”

“So, as you very well know, every medicine, every drug, aspirin, lipitor, you know, Prozac, works by binding to something.”

“And so, the key has to be a little bit of a wriggle of a key that goes in, but basically it's all aspirin is a key. We know the lock, lipitor is a key, we know the lock, Prozac is a key, we know the lock, and so forth. All right, so in the past, we had two ways of looking for keys.”

“I was just about to say, will there be a drug? Just as I can give you lipitor today long before you have a heart attack, and I can give it to you with an ACE inhibitor if your blood pressure is high, these two molecules will prevent you from having a heart attack.”

“chemo prevention is going to be as simple. So remember, lipitor blocks decreases your LDL levels and Losartan or whatever ACE inhibitor or ARB inhibits your capacity to have high blood pressure by acting on your kidneys, hormonal system.”

“and we have treatments for all of them. You can take aspirin lipitor and PCSK9. You can take like 17 drugs now. That's right. So if you don't smoke, if you take whatever drugs are necessary to stay insulin sensitive, if you obliterate your”

“And good experimental people can do fussy experimental science. Sid, the GLP-1 agonists, while potentially in the very near term, will transiently raise insulin levels to aid with glucose disposal, ultimately tend to reduce hyperinsulinemia.”

“I think it's a beautiful study. It would be a beautiful study. You would randomize to patients with on GLP-1 versus not GLP-1. You would study their insulinemic response versus their weight loss response.”

“And just ask the question: listen, if people who are on GLP-1 versus not GLP-1, you know, is there a lower risk of endometrial cancer? Now, see, I prefer the experimental approach here. Yeah, not just because of time.”

“And I think someone should fund this study. I mean, you know, if it's not the NIH, if it's not the Eli Lilly or Novo or whoever else is now making, you know, any of the GLP-1s, you know, any of the people, anyone in the audience who's, you know, interested in”

“Yeah, I mean, you know, as I said, we have, and we have some tools. We have the GLP ones, for instance, in obesity and potentially in inflammation. So that's a trial that I would like to watch very, very carefully. I hope someone listening to us today, by the way, has taken, has become motivated by that idea.”

“we know that there are a radical new set of medicines on the horizon. You've seen cases of pancreatic cancer treated with the Daraxonrasib, a new medicine against one of those killer genes called RAS. It's extended the life of patients. We've seen videos of these patients on television. They're now living with pancreatic cancer, you know, months, if not years, after the cancer has spread,”

“So now we're not talking about the immune system. We're talking about small molecules, locks and keys, keys that go and shut off the lock, Daraxonrasib, nasty side effects. You've seen the senator with those lesions in the face. I'm sorry about those nasty side effects.”

“The real interesting question is: what's Daraxonrasib going to do to adjuvant therapy? So, a patient comes in, not the senator. The patient comes in, has painless jaundice, classic example of pancreatic cancers, found to have a big lump Goomba in the traffic intersection of all of this, goes through a Whipple.”

“And now we put them, they have KRAS mutation. We put them on Daraxonrasib, then ask the question: are they better or worse off? Is that trial being done? It'll be done if it's not in the case. I mean, is it in the works?”

“My guest this week is Dr. Siddhartha Mukherjee, a returning guest to the drive. Sid is a physician, oncologist, researcher, and a Pulitzer Prize-winning author of The Emperor of All Maladies, as well as other books, The Gene and The Song of the Cell.”

“We begin our conversation with cancer as this is the 15-year anniversary, it's hard to believe, of his remarkable book, An Emperor of All Maladies. We talk about where it comes from, how much it is driven by genetics versus chance, the challenges of detecting it early, and how treatment has advanced”

“Sid, awesome to see you, as always. And it's hard to believe it's been 15 years since Emperor of All Maladies. I remember reading it as soon as it came out, and that I think makes me feel a little old that 15 years has gone by so quickly.”

“here having another discussion in 15 years, looking back and saying, God, I can't believe it was 30 years ago you wrote Emperor of All Maladies. If you had to predict what we're going to say in 15 years that is true about cancer that is not yet true today, what do you realistically think that might be?”

“paper aimed at thymic regeneration. And it was a little bit of a kitchen sink approach, right? They gave these patients growth hormone and metformin and a whole cocktail of things. And on imaging, they showed, hey, look, these, you know, these in the patients who got this, and by the way, it was even worse because I think it was an open label study, so there wasn't even a randomization.”

“Because I don't even recall the rationale for metformin growth hormone and DHEA or whatever they were giving. Have you followed this space at all? And are there molecular attempts at this?”

“I was just about to say, will there be a drug? Just as I can give you Lipitor today, long before you have a heart attack, and I can give it to you with an ACE inhibitor if your blood pressure is high. These two molecules will prevent you from having a heart attack.”

“And Losartan or whatever ACE inhibitor or ARB inhibits your capacity to have high blood pressure.”

“Yes. And while our therapies are still limited, we have colchicine. Now, it's a crude drug, but there's evidence that if you have, you know, if you're... We have better meds than Colchicine, by the way.”

“So two good examples are the use of a drug called Enhertu in breast cancer, which works even after many, many lines of therapies have stopped working.”

“Okay, so we get that. That's standard immunotherapy. Keytruda is one example of that. There are other ones. Okay, a CAR T is a slightly different variant of that. A CAR T is a variant in which I say, okay, I'm going to override all of those signals.”

“chemo prevention is going to be as simple. So remember, lipitor blocks decreases your LDL levels and Losartan or whatever ACE inhibitor or ARB inhibits your capacity to have high blood pressure by acting on your kidneys, hormonal system.”

“obviously, reduce exposure to these forever chemicals, and based on no evidence whatsoever, use probiotics to, and probiotics are cheap. I don't mean go buy like very fancy, I just mean have live yogurt.”

“The Gene and The Song of the Cell. I wanted to have Sid back on because, frankly, there are few people who can move as easily between the molecular details of a disease and the much bigger questions of why we age and what we might be able to do about it.”

“The Gene and The Song of the Cell. I wanted to have Sid back on because, frankly, there are few people who can move as easily between the molecular details of a disease and the much bigger questions of why we age and what we might be able to do about it.”

“I don't mean go buy like very fancy, I just mean have live yogurt. Yogurt, yeah. Yeah, at least once a week so that you can replace your probiotics. So, we've touched a little bit on AI, and I know that it's something that we are both thinking a lot about.”