The study views cancer therapy as a game between the treating physician and the cancer cells undergoing therapy. The physician “plays” the game by applying a treatment while the cancer cells “play” by evolving new properties that allow them to overcome the toxicity of the drugs administered by the physician. The analysis challenges the decades old standard of treatment for metastatic cancers in which drugs are typically administered continuously at the maximum-tolerated dose (MTD). Instead, the team concluded that treating physicians can exploit their understanding of evolution and their role as the “leader” in the game to apply therapy more strategically to delay or prevent the cancer cells from developing resistance, and ultimately improve patient outcomes.

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Physician leads

The research team used evolutionary game theory to study the interactions between physicians and cancer cells. In their study, the team demonstrates how the physician can engage the cancer cells in a leader-follower game (often described as a “Stackelberg” game after the German mathematician who extensively investigated the dynamics in the mid-20^th century).  The physician, who chooses and applies a treatment, is the leader in this game, as he or she has the advantage of “playing first”, while the cancer cells adapt to this treatment and are therefore the followers.  Physician’s additional critical advantage is that only the physician is sentient and, therefore, can understand and use the principles of evolution. In contrast, cancer cells, like all evolving populations, can only adapt to current conditions – they cannot think and, therefore, can never anticipate the future or adapt to a treatment that has yet to be applied.

War on cancer

The standard practice for treatment of metastatic cancer, widely accepted for over half a century, does not exploit these advantages. Current therapies typically apply treatments at the maximum-tolerated dose (MTD), which is the largest dose a patient can withstand without excessive toxicity. These doses, often given continually or in repeated cycles, are altered only in the event of unacceptable toxicity or clear evidence of tumour progression.  While killing as many cancer cells with the highest possible dose of drug is intuitively appealing in the “war” on cancer, it may be evolutionarily unwise.  MTD is likely to accelerate the development of resistance leading to treatment failure.  So, even when the initial response to high dose therapy is very favourable in metastatic cancers, resistance typically develops and the cancer recurs.