Fig. 1. Examples of evolutionary cancer treatment strategies.

Panel A demonstrates therapy for a mixed population of sensitive and resistant cells. Adaptive therapy reduces the tumor population but explicitly maintains a small population of treatment-sensitive cells. Once an initial tumor response is achieved, therapy is discontinued. In the absence of treatment, sensitive cells have a fitness advantage and will proliferate at the expense of the resistant cells. While the resistant cells will eventually dominate, the goal is to maintain tumor control with therapy for the longest possible time period.

Panel B illustrates a double bind approach in which the resistance mechanism to one therapy can be treated with the other therapy (see text for example). Combining the two therapies will simply select for an alternative adaptive pathway and only slightly delays time to progression (not shown). However, by administering them in sequence, the evolutionary dynamics (termed “predator facilitation”) forces the cancer cells to oscillate between phenotypes. This is an evolutionarily futile cycle which can permit long term control of an invasive species.