In a dramatic demonstration of the power of evolutionary thinking for cancer research, adaptive therapy has been shown to be substantially superior to regular treatment for metastatic prostate cancer. Only 1 of 11 patients in the adaptive therapy cohort showed radiographic disease progression, compared to 14 of 16 in the usual treatment condition. The adaptive therapy group got cumulative drug doses less than half that of the usual group.
Zhang, J., Cunningham, J. J., Brown, J. S., & Gatenby, R. A. (2017). Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer. Nature Communications 8, Article number: 1816 (2017) doi:10.1038/s41467-017-01968-5
ABSTRACT: Abiraterone treats metastatic castrate-resistant prostate cancer by inhibiting CYP17A, an enzyme for testosterone auto-production. With standard dosing, evolution of resistance with treatment failure (radiographic progression) occurs at a median of ~16.5 months. We hypothesize time to progression (TTP) could be increased by integrating evolutionary dynamics into therapy. We developed an evolutionary game theory model using Lotka–Volterra equations with three competing cancer “species”: androgen dependent, androgen producing, and androgen independent. Simulations with standard abiraterone dosing demonstrate strong selection for androgen-independent cells and rapid treatment failure. Adaptive therapy, using patient-specific tumor dynamics to inform on/off treatment cycles, suppresses proliferation of androgen-independent cells and lowers cumulative drug dose. In a pilot clinical trial, 10 of 11 patients maintained stable oscillations of tumor burdens; median TTP is at least 27 months with reduced cumulative drug use of 47% of standard dosing. The outcomes show significant improvement over published studies and a contemporaneous population.