Androgens and Prostate Cancer Bone Metastases: Effects on Both the Seed and the Soil

Androgens are essential for normal prostate development and are necessary, but not sufficient, for the development of prostate cancer (PCa). Androgen deprivation therapy has long been the mainstay of treatment for PCa bone metastases, providing palliation of symptoms in the majority of patients, followed by relapse and progression. The majority of published preclinical studies demonstrate a stimulatory effect of androgens and androgen receptor signaling on the multistep process of PCa bone metastases, including androgenic promotion of local PCa growth, angiogenesis, invasion, bone targeting, stimulation of PCa growth factors that enhance osteoclastogenesis, and enhancement of Wnt signaling in osteoblasts.