Oct 25, 2021
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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