Abstract B014: Simulating prostate cancer stem cell dynamics to predict patient-specific sensitivity or resistance to intermittent androgen-deprivation therapy

Abstract

Abstract Intermittent androgen suppression is an attractive treatment approach for biochemically recurrent locally advanced prostate cancer to delay evolution of treatment resistance (PMID: 16783817). We developed a mathematical model of prostate cancer stem cell dynamics during therapy as a plausible mechanism of resistance evolution. We simulate division dynamics of cancer stem cells, non-stem cancer cells, and PSA concentration and generate highly accurate model fits to the longitudinal data of 55 patients undergoing 2-4 cycles of intermittent androgen suppression. We analyze model dynamics to identify cancer stem cell proliferation patterns that correlate with patient outcomes, and score model predictive power to accurately forecast evolution of resistance in individual patients. The presented framework may contribute to identifying patients who do and do not develop resistance to intermittent androgen suppression. The obtained predictive power on a retrospective data set warrants prospective evaluation in a clinical setting. Citation Format: Renee Brady, John Nagy, John Nagy, Heiko Enderling. Simulating prostate cancer stem cell dynamics to predict patient-specific sensitivity or resistance to intermittent androgen-deprivation therapy [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B014.