Integrating evolutionary dynamics into treatment of metastatic castrate-resistant prostate cancer

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…

• JS
  James S. McDonnell Foundation
• MC
  Moffitt Cancer Center

  Awards: U54CA143970-05, U54CA143970, P30-CA076292, CA076292
• EC
  European Commission

  Award: 690817
• NI
  National Institutes of Health

  Awards: NCI U54CA143970-05, U54CA143970, R01CA170595, NIH/NCI U54CA143970-05, P30-CA076292, U54CA143970-05
• NC
  National Cancer Institute

  Awards: NIH/NCI U54CA143970-05, P30-CA076292, R01CA170595, U54CA143970, U54CA143970-05, CA076292