#181 - Robert Gatenby, M.D.: Viewing cancer through an evolutionary lens and why this offers a radically different approach to treatment

The Peter Attia Drive

Robert (Bob) Gatenby is a radiologist who specializes in exploring theoretical and experimental models of evolutionary dynamics in cancer and cancer drug resistance. He has developed an adaptive therapy approach for treating cancer which has shown promise in improving survival times with less cumulative drug use. In this episode, Bob explains what brought him into medicine, his search for organizing principles from which to understand cancer, and the mathematical modeling of other complex systems that led him to model the dynamics of tumor cell changes in cancer. He discusses his pilot clinical trial treating metastatic prostate cancer, in which he used an evolutionary game theory model to analyze patient-specific tumor dynamics and determine the on/off cycling of treatment. He describes how altering chemotherapy to maximize the fitness ratio between drug-sensitive and drug-resistant cancer cells can increase patient survival and explains how treatment of metastatic cancer may be improved using adaptive therapy and strategic sequencing of different chemotherapy drugs. We discuss:

• Bob’s unlikely path to medicine and disappointment with his medical school experience [1:45];
• Rethinking the approach to cancer: using first principles and applying mathematical models [12:15];
• Relating predator-prey models to cancer [26:30];
• Insights into cancer gathered from ecological models of pests and pesticides [32:15];
• Bob’s pilot clinical trial: the advantages of adaptive therapy compared to standard prostate cancer treatment [41:45];
• New avenues of cancer therapy: utilizing drug-sensitive cancer cells to control drug-resistant cancer cells [48:15];
• The vulnerability of small populations of cancer cells and the problem with a “single strike” treatment approach [56:00];
• Using a sequence of therapies to make cancer cells more susceptible to targeted treatment [1:05:00];
• How immunotherapy fits into the cancer treatment toolkit [1:15:30];
• Why cancer spreads, where it metastasizes, and the source-sync trade off [1:20:15];
• Defining Eco- and Evo-indices and how they can be used to make better clinical decisions [1:29:45];
• Advantages of early screening for cancer [1:40:15];
• Bob’s goals for follow-ups after the success of his prostate cancer trial [1:42:15];
• Treatment options for cancer patients who have “failed therapy” [1:51:15];
• More.

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