Applying Game Theory to Cancer Treatment and Clinics Trials

 

When members of Cancer ABCs staff were reviewing a paper published in Jama Review, “Optimizing Cancer Treatment Using Game Theory,” they quickly realized how potentially important this paper could be for people with cancer and how current treatment protocols and clinical trials ignore its many excellent points.  The paper explores how we ignore the basic and proven principles of “Game Theory” as it applies to our clinical treatment of, or perhaps our failure to properly treat cancer.  

The paper points out that systemic treatment for metastatic cancer is often initially successful. However, we know in many instances cancer will develop resistance to the treatment, or said another way, cancer finds ways to use the diverse adaptive strategies encoded in the human genome to beat the treatment. 

The Darwinian dynamics of resistance and natural selection which has served us well and allowed us to develop into who we are today also pose formidable barriers to all forms of single, extended, systemic cancer treatment.  Our current clinical trial design and our current treatment protocols rarely, if ever consider these basic and undisputable Darwinian dynamics. These dynamics will almost always support the development of treatment resistance.

If you apply basic game theory to cancer treatment, you can sum up treatment protocols as a theoretic contest between the therapy as delivered by an oncologist and the cancer cell’s natural Darwinian resistance strategies. 

Cancer cells, like all evolving organisms, can only adapt to current conditions or current treatments; they can neither anticipate nor evolve adaptations to the treatments not yet applied.   Cancer must follow a distinctive leader-follower (or “Stackelberg”) type game plan where the rational “leader” or the oncologist plays first and the “follower,” the cancer cells then respond and adapt to the therapy.

When the leader oncologist repeatedly plays the game with a fixed strategy, as we often do, by administering the same drug(s) until disease progression, the opposing cancer cells continuously evolve successful adaptive responses or resistance through basic Darwinian principles.   The cancer is then the new game leader and the ultimate game-winner.

The application of Game Theory to cancer treatment should be encouraging us to rethink our basic treatment protocols of using single, consistent treatments until it fails, or how we play the game.  Game theory dictates that we instead exploit the advantages of being the game leader in the cancer treatment game, and likely improve outcomes.  We should be considering do this by maintaining the role of game leader by adopting more dynamic treatment protocols that integrate the basic Darwinian principles into our treatment protocols. 

An interesting example of this Game Theory type of treatment protocol is BAT for advanced prostate cancer. Prostate cancer relies on testosterone to feed cancer.  Current, traditional therapy for advanced prostate cancer is to eliminate and block the testosterone (ADT or Hormone Therapy), so it cannot feed the cancer until it fails when we add an additional treatment.  ADT has a limited life as the cancer cells use Darwinian strategies to beat the treatment.  A small number of clinicians are pushing the envelope and have been experimenting with using the game theory principles by instead constantly modifying testosterone levels from castration to raising testosterone levels to the extremes, doing this again and again.  Informal data shows that this BAT treatment protocol might be effective.  

Applying game theory to cancer treatment involves a new way to view how we deal with cancer. Changing basic thought and direction is hard, but maybe we should be evaluating this approach in cancer clinical trials and treatment.

Discuss this type of treatment with your oncologist.  Are there ways that you might be able to apply game theory to your cancer treatment?