The Evolutionary Impact of Androgen Levels on Prostate Cancer in a Multi-Scale Mathematical Model

The study developed a multi-scale mathematical model to explore the impact of androgen levels on prostate cancer. It found that low androgen environments, due to low serum testosterone or 5α-reductase inhibition, increased the selection for androgen receptor (AR) overexpression in prostate epithelial cells, leading to more aggressive and therapy-resistant cancers. High androgen levels weakly protected against AR overexpression. The findings suggested that while low androgen might delay cancer onset, it could result in more aggressive cancers later in life, aligning with clinical observations that low testosterone levels predict poorer responses to androgen deprivation therapy. The study emphasized the need for long-term follow-up in patients treated with 5α-reductase inhibitors like finasteride.