View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter In this episode, Peter welcomes back Dr. Siddhartha Mukherjee, a physician, oncologist, researcher, and the Pulitzer Prize-winning author of The Emperor of All Maladies. Fifteen years after the book was first published, Sid released an updated edition. This conversation examines what has changed in our understanding of cancer—not only in how we treat it, but in how we think about its causes, prevention, detection, and biology. Sid explores the contributions of genetics, environmental exposures, random mutations, and inflammation to cancer risk, including the emerging role of hyperinsulinemia and metabolism. He discusses why detecting cancer early remains so difficult, particularly in pancreatic cancer, and how advances in immunotherapy, CAR T cell therapy, and targeted treatments such as KRAS inhibitors are changing the treatment landscape. The conversation then broadens beyond cancer to what Sid calls "regenerative failure"—the declining ability of tissues to repair and replenish themselves with age. Peter and Sid explore how this process may contribute to conditions such as osteoarthritis, and whether longevity should be approached less as the prevention of individual diseases and more as the preservation of regenerative capacity. Sid weighs in on the potential for chemoprevention, metabolic interventions, and AI to transform cancer prevention and treatment. Finally, they discuss what it would take to develop meaningful biomarkers of longevity that could ultimately help to extend human healthspan and lifespan. We discuss: What oncology has learned in the 15 years since The Emperor of All Maladies was published [2:45]; The contributions of genetic risk, bad luck, and inflammation to cancer [14:45]; The role of metabolism and hyperinsulinemia in cancer [31:00]; Osteoarthritis: the role of inflammation and regenerative stem cells [40:45]; How cancer escapes the immune system—the subtleties of neoantigens and immune checkpoints [49:45]; AI and the thymus as a predictor of longevity, and T cell aging and immune regeneration [57:15]; How CAR T cell therapy works and why solid tumors are harder to treat [1:04:00]; Targeting KRAS in pancreatic cancer [1:10:45]; The rise of colorectal cancer in younger adults [1:19:15]; How AI may transform drug discovery [1:23:00]; The future of cancer prevention: chemoprevention [1:33:15]; Challenging the current model of longevity—disease prevention versus targeting regenerative failure [1:37:45]; The need for a biomarker of longevity—comparing geroscience to atherosclerosis [1:50:30]; Clinical trials targeting cancer metabolism [1:56:00]; What Sid is currently writing about and a glimpse into his writing process [1:58:00]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube
