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

Siddhartha Mukherjee (0:11)

Hey, everyone.

Peter Attia (0:11)

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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. 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. 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. Before broadening our discussion to what Sid calls regenerative failure, the declining ability of our tissues to repair and replenish themselves as we age.

Throughout this episode, we discuss how genetics, environment, and random mutations contribute to cancer risk. We talk about the challenges of cancer screening and early detection across all cancers, but especially pancreatic cancer, why aging isn't simply the accumulation of diseases, but also the loss of our ability to regenerate, how declining stem cell function may contribute to osteoarthritis and other age-related conditions, the relationship between inflammation, the immune system, and regenerative failure, what it would take to meaningfully extend human health span and lifespan, and how AI may help us better understand and potentially address the biology of aging and cancer. So without further delay, please enjoy my conversation with Dr. Sid Mukherjee.

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. If we take a step back, what would you say is true today in the field of oncology that was not true? Or maybe phrased another way, what do we know today about cancer that we did not know when you published this remarkable book?

Siddhartha Mukherjee (3:23)

Well, Peter, first of all, thank you for having me. It's been a pleasure throughout. We've spoken in the middle and learned more about cancer in the middle. Let me divide it very simply into three large sections and ask the question, what do we know more about early diagnosis or prevention, early detection, and treatment? So three broad categories.

So prevention, what do we know about prevention? Well, good news and bad news. The good news is that we know a lot more about how cancer can arise not just out of being exposed to the traditional carcinogens, the cancer-causing agents, that you and I know very much about, x-rays and benzene and tobacco, etc. So we now know that there is almost certainly inflammatory states that cause cancer. We know a lot about the nature of these inflammatory states.

We know that there is a kind of a gun and trigger effect, the gun being the inflammatory state, the trigger being the mutations that cause cancer, or a mix of some states like that. The bad news is that we are still early in that story. In other words, I can't look at a person, a patient, my own patient, and say to them, oh my goodness, I know that you're in an inflammatory state. You have that inflammatory state, which is going to be procarcinogenic. I don't have a biomarker in the same sense that I have a biomarker for, let's say cardiovascular disease being hypertension or high cholesterol levels. I don't have a high cholesterol for cancer. Almost certainly, we will find it. We will find that high cholesterol for cancer, and we will find people who are at risk and put them in clinical trials to follow them and figure out how we can prevent cancer. The second piece of good news in prevention, we're still in prevention, is that we now know much more about genetics.